Variant chr9-133351795-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003172.4(SURF1):c.*118T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 1,144,576 control chromosomes in the GnomAD database, including 3,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 333 hom., cov: 33)

Exomes 𝑓: 0.073 ( 2985 hom. )

Consequence

SURF1
NM_003172.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.229

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-133351795-A-G is Benign according to our data. Variant chr9-133351795-A-G is described in ClinVar as [Benign]. Clinvar id is 912544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SURF1	NM_003172.4 linkuse as main transcript	c.*118T>C		3_prime_UTR_variant	9/9	ENST00000371974.8
SURF1	NM_001280787.1 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SURF1	ENST00000371974.8 linkuse as main transcript	c.*118T>C		3_prime_UTR_variant	9/9	1	NM_003172.4	P1	Q15526-1
SURF1	ENST00000615505.4 linkuse as main transcript			downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0563

AC:

8573

AN:

152206

Hom.:

334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0157

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0477

Gnomad ASJ

AF:

0.0796

Gnomad EAS

AF:

0.0190

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.0592

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0870

Gnomad OTH

AF:

0.0602

GnomAD4 exome

AF:

0.0727

AC:

72174

AN:

992252

Hom.:

2985

Cov.:

AF XY:

0.0708

AC XY:

35690

AN XY:

503816

show subpopulations

Gnomad4 AFR exome

AF:

0.0126

Gnomad4 AMR exome

AF:

0.0367

Gnomad4 ASJ exome

AF:

0.0765

Gnomad4 EAS exome

AF:

0.0238

Gnomad4 SAS exome

AF:

0.0212

Gnomad4 FIN exome

AF:

0.0599

Gnomad4 NFE exome

AF:

0.0850

Gnomad4 OTH exome

AF:

0.0698

GnomAD4 genome

AF:

0.0563

AC:

8570

AN:

152324

Hom.:

333

Cov.:

AF XY:

0.0550

AC XY:

4094

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0157

Gnomad4 AMR

AF:

0.0477

Gnomad4 ASJ

AF:

0.0796

Gnomad4 EAS

AF:

0.0191

Gnomad4 SAS

AF:

0.0209

Gnomad4 FIN

AF:

0.0592

Gnomad4 NFE

AF:

0.0870

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0710

Hom.:

Bravo

AF:

0.0546

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Leigh syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.1

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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