Variant chr9-133332015-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006753.6(SURF6):c.940G>A(p.Val314Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,448,044 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SURF6
NM_006753.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.36

Variant links:

Genes affected

SURF6 (HGNC:11478): (surfeit 6) This gene encodes a conserved protein that is localized to the nucleolus. The encoded protein may function as a nucleolar-matrix protein with nucleic acid-binding properties. There is a pseudogene for this gene on chromosome Y. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

SURF6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38296443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SURF6	NM_006753.6 linkuse as main transcript	c.940G>A	p.Val314Met	missense_variant	5/5	ENST00000372022.6	NP_006744.2
SURF6	NM_001278942.2 linkuse as main transcript	c.*345G>A		3_prime_UTR_variant	5/5		NP_001265871.1
SURF6	NR_103874.2 linkuse as main transcript	n.943G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SURF6	ENST00000372022.6 linkuse as main transcript	c.940G>A	p.Val314Met	missense_variant	5/5	1	NM_006753.6	ENSP00000361092	P1
SURF6	ENST00000468290.1 linkuse as main transcript	n.726G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1448044

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000831

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.940G>A (p.V314M) alteration is located in exon 5 (coding exon 5) of the SURF6 gene. This alteration results from a G to A substitution at nucleotide position 940, causing the valine (V) at amino acid position 314 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.048

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.86

MutationAssessor

Pathogenic

3.3

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.8

REVEL

Benign

0.23

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.050

Polyphen

0.98

Vest4

0.41

MutPred

0.48

Gain of methylation at K309 (P = 0.1128);

MVP

0.40

MPC

0.29

ClinPred

0.91

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.045

gMVP

0.41

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