dbSNP rs587598397: SURF1:c.54+10G>C (chr9-133356390-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003172.4(SURF1):c.54+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,238,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

SURF1
NM_003172.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 9-133356390-C-G is Benign according to our data. Variant chr9-133356390-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2984476.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SURF1	NM_003172.4 link	c.54+10G>C	intron_variant	Intron 1 of 8	ENST00000371974.8	NP_003163.1	Q15526-1E5KRX5
SURF1	NM_001280787.1 link	c.-222+10G>C	intron_variant	Intron 1 of 7		NP_001267716.1	Q15526A0A087WYS9
SURF2	NM_017503.5 link	c.-203C>G	upstream_gene_variant		ENST00000371964.5	NP_059973.4	Q15527
SURF2	NM_001278928.2 link	c.-203C>G	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>C		intron_variant	Intron 1 of 8	1	NM_003172.4	ENSP00000361042.3		Q15526-1
SURF2	ENST00000371964.5 link	c.-203C>G		upstream_gene_variant		1	NM_017503.5	ENSP00000361032.4		Q15527

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000161

AC:

AN:

1238642

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

607026

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24364

American (AMR)

AF:

0.00

AC:

AN:

16130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18996

East Asian (EAS)

AF:

0.0000737

AC:

AN:

27132

South Asian (SAS)

AF:

0.00

AC:

AN:

59020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3538

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1008318

Other (OTH)

AF:

0.00

AC:

AN:

50912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Leigh syndrome

Benign:1

Mar 16, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.8

(source)

DANN

Benign

0.53

PhyloP100

0.39

PromoterAI

-0.021

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over