Variant 11-65115326-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000279263.14(TM7SF2):c.905A>G(p.Tyr302Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,990 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

TM7SF2
ENST00000279263.14 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Variant links:

Genes affected

TM7SF2 (HGNC:11863): (transmembrane 7 superfamily member 2) Enables delta14-sterol reductase activity. Involved in cholesterol biosynthetic process. Located in endoplasmic reticulum. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

TM7SF2 links:

TM7SF2 (HGNC:):

TM7SF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TM7SF2	NM_003273.6 linkuse as main transcript	c.905A>G	p.Tyr302Cys	missense_variant	8/10	ENST00000279263.14	NP_003264.2	O76062-1A0A024R577
TM7SF2	NM_001277233.2 linkuse as main transcript	c.893-150A>G		intron_variant			NP_001264162.1	O76062-2
TM7SF2	NR_102367.2 linkuse as main transcript	n.994A>G		non_coding_transcript_exon_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TM7SF2	ENST00000279263.14 linkuse as main transcript	c.905A>G	p.Tyr302Cys	missense_variant	8/10	1	NM_003273.6	ENSP00000279263.7		O76062-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249568

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000414

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

Feb 16, 2023

The c.905A>G (p.Y302C) alteration is located in exon 8 (coding exon 8) of the TM7SF2 gene. This alteration results from a A to G substitution at nucleotide position 905, causing the tyrosine (Y) at amino acid position 302 to be replaced by a cysteine (C). 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

0.062

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

D;D;D;D;D;D

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.95

D;T;D;T;D;D

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.68

D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.0

.;M;.;.;.;.

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-4.1

D;D;D;D;D;D

REVEL

Pathogenic

0.81

Sift

Uncertain

0.013

D;T;D;T;D;D

Sift4G

Uncertain

0.038

D;T;T;T;T;D

Polyphen

1.0

.;D;.;.;.;.

Vest4

0.32

MutPred

0.77

.;Loss of MoRF binding (P = 0.0933);.;.;.;.;

MVP

0.99

MPC

0.48

ClinPred

0.27

GERP RS

3.8

Varity_R

0.25

gMVP

0.74

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