rs587781184

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP3BP6BS1BS2

The NM_003172.4(SURF1):c.54+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 1,390,498 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0029 ( 5 hom., cov: 34)

Exomes 𝑓: 0.0041 ( 14 hom. )

Consequence

SURF1
NM_003172.4 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 0.389

Publications

0 publications found

Variant links:

Genes affected

SURF1 (HGNC:11474): (SURF1 cytochrome c oxidase assembly factor) This gene encodes a protein localized to the inner mitochondrial membrane and thought to be involved in the biogenesis of the cytochrome c oxidase complex. The protein is a member of the SURF1 family, which includes the related yeast protein SHY1 and rickettsial protein RP733. The gene is located in the surfeit gene cluster, a group of very tightly linked genes that do not share sequence similarity, where it shares a bidirectional promoter with SURF2 on the opposite strand. Defects in this gene are a cause of Leigh syndrome, a severe neurological disorder that is commonly associated with systemic cytochrome c oxidase deficiency. [provided by RefSeq, Jul 2008]

SURF1 links:

SURF2 (HGNC:11475): (surfeit 2) This gene shares a bidirectional promoter with surfeit 1 (SURF1; GeneID: 6834), which is located on the opposite strand. It encodes a conserved protein that is expressed in a variety of tissues. [provided by RefSeq, Jul 2013]

SURF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 9-133356390-C-T is Benign according to our data. Variant chr9-133356390-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 139379.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00285 (433/151860) while in subpopulation SAS AF = 0.00455 (22/4834). AF 95% confidence interval is 0.00383. There are 5 homozygotes in GnomAd4. There are 206 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SURF1	NM_003172.4 link	c.54+10G>A	intron_variant	Intron 1 of 8	ENST00000371974.8	NP_003163.1	Q15526-1E5KRX5
SURF1	NM_001280787.1 link	c.-222+10G>A	intron_variant	Intron 1 of 7		NP_001267716.1	Q15526A0A087WYS9
SURF2	NM_017503.5 link	c.-203C>T	upstream_gene_variant		ENST00000371964.5	NP_059973.4	Q15527
SURF2	NM_001278928.2 link	c.-203C>T	upstream_gene_variant			NP_001265857.1	Q15527

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SURF1	ENST00000371974.8 link	c.54+10G>A		intron_variant	Intron 1 of 8	1	NM_003172.4	ENSP00000361042.3		Q15526-1
SURF2	ENST00000371964.5 link	c.-203C>T		upstream_gene_variant		1	NM_017503.5	ENSP00000361032.4		Q15527

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

433

AN:

151754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.000191

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00423

Gnomad OTH

AF:

0.00336

GnomAD2 exomes

AF:

0.00535

AC:

127

AN:

23718

AF XY:

0.00554

show subpopulations

Gnomad AFR exome

AF:

0.00455

Gnomad AMR exome

AF:

0.00319

Gnomad ASJ exome

AF:

0.0213

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00499

Gnomad OTH exome

AF:

0.00802

GnomAD4 exome

AF:

0.00414

AC:

5127

AN:

1238638

Hom.:

Cov.:

AF XY:

0.00411

AC XY:

2493

AN XY:

607026

show subpopulations

African (AFR)

AF:

0.000451

AC:

AN:

24364

American (AMR)

AF:

0.00254

AC:

AN:

16130

Ashkenazi Jewish (ASJ)

AF:

0.0180

AC:

341

AN:

18996

East Asian (EAS)

AF:

0.00

AC:

AN:

27132

South Asian (SAS)

AF:

0.00319

AC:

188

AN:

59020

European-Finnish (FIN)

AF:

0.000198

AC:

AN:

30232

Middle Eastern (MID)

AF:

0.00876

AC:

AN:

3538

European-Non Finnish (NFE)

AF:

0.00427

AC:

4307

AN:

1008314

Other (OTH)

AF:

0.00397

AC:

202

AN:

50912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

274

547

821

1094

1368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00285

AC:

433

AN:

151860

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

206

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.000554

AC:

AN:

41488

American (AMR)

AF:

0.00210

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00455

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000191

AC:

AN:

10462

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00423

AC:

287

AN:

67880

Other (OTH)

AF:

0.00332

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00420

Hom.:

Bravo

AF:

0.00295

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SURF1: BS2 -

Oct 21, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 02, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Leigh syndrome

Uncertain:1Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 01, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.39

PromoterAI

-0.084

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.67

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.67

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over