dbSNP rs782659731: SURF1:c.54+9_54+22delCGGGTGCGGGGTGC (chr9-133356377-CGCACCCCGCACCCG-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_003172.4(SURF1):c.54+9_54+22delCGGGTGCGGGGTGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SURF1
NM_003172.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.946

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:

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ACMG classification

Classification was made for transcript

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

BP6

Variant 9-133356377-CGCACCCCGCACCCG-C is Benign according to our data. Variant chr9-133356377-CGCACCCCGCACCCG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 420446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SURF1	NM_003172.4 link	c.54+9_54+22delCGGGTGCGGGGTGC	intron_variant	Intron 1 of 8	ENST00000371974.8	NP_003163.1
SURF1	NM_001280787.1 link	c.-222+9_-222+22delCGGGTGCGGGGTGC	intron_variant	Intron 1 of 7		NP_001267716.1
SURF2	NM_017503.5 link	c.-215_-202delGCACCCCGCACCCG	upstream_gene_variant		ENST00000371964.5	NP_059973.4
SURF2	NM_001278928.2 link	c.-215_-202delGCACCCCGCACCCG	upstream_gene_variant			NP_001265857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SURF1	ENST00000371974.8 link	c.54+9_54+22delCGGGTGCGGGGTGC		intron_variant	Intron 1 of 8	1	NM_003172.4	ENSP00000361042.3
SURF2	ENST00000371964.5 link	c.-215_-202delGCACCCCGCACCCG		upstream_gene_variant		1	NM_017503.5	ENSP00000361032.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00172

AC:

AN:

10440

AF XY:

0.00163

show subpopulations

Gnomad AFR exome

AF:

0.0410

Gnomad AMR exome

AF:

0.00293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1241500

Hom.:

AF XY:

0.00

AC XY:

AN XY:

607898

African (AFR)

AF:

0.00

AC:

AN:

24428

American (AMR)

AF:

0.00

AC:

AN:

16342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18604

East Asian (EAS)

AF:

0.00

AC:

AN:

27612

South Asian (SAS)

AF:

0.00

AC:

AN:

59206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3568

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1010844

Other (OTH)

AF:

0.00

AC:

AN:

50984

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.00122

AC:

AN:

3292

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 01, 2016

GeneDx

Significance:Likely 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. -

Leigh syndrome

Benign:1

Feb 03, 2025

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

PhyloP100

0.95

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over