rs587781184

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PP3

Splicing scoreres supports a deletorius 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 id is 139379.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=2, Uncertain_significance=1}. Variant chr9-133356390-C-T is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

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

GnomAD3 exomes

AF:

0.00535

AC:

127

AN:

23718

Hom.:

AF XY:

0.00554

AC XY:

AN XY:

14446

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 SAS exome

AF:

0.00373

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

Gnomad4 AFR exome

AF:

0.000451

Gnomad4 AMR exome

AF:

0.00254

Gnomad4 ASJ exome

AF:

0.0180

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00319

Gnomad4 FIN exome

AF:

0.000198

Gnomad4 NFE exome

AF:

0.00427

Gnomad4 OTH exome

AF:

0.00397

GnomAD4 genome

AF:

0.00285

AC:

433

AN:

151860

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

206

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.00210

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.000191

Gnomad4 NFE

AF:

0.00423

Gnomad4 OTH

AF:

0.00332

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

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 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SURF1: BS2 -

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

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

DANN

Benign

0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over