Variant chr12-26974200-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 NM_016551.3(TM7SF3):c.1478T>C(p.Met493Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TM7SF3
NM_016551.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.88

Variant links:

Genes affected

TM7SF3 (HGNC:23049): (transmembrane 7 superfamily member 3) Involved in cellular response to unfolded protein; negative regulation of programmed cell death; and positive regulation of insulin secretion. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TM7SF3 links:

(HGNC:):

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
TM7SF3	NM_016551.3 linkuse as main transcript	c.1478T>C	p.Met493Thr	missense_variant	12/12	ENST00000343028.9
TM7SF3	XM_017019463.3 linkuse as main transcript	c.1568T>C	p.Met523Thr	missense_variant	12/12
TM7SF3	XM_047428990.1 linkuse as main transcript	c.1415T>C	p.Met472Thr	missense_variant	11/11
TM7SF3	XM_005253391.5 linkuse as main transcript	c.1325T>C	p.Met442Thr	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TM7SF3	ENST00000343028.9 linkuse as main transcript	c.1478T>C	p.Met493Thr	missense_variant	12/12	1	NM_016551.3	P1
	ENST00000500632.1 linkuse as main transcript	n.960+1655A>G		intron_variant, non_coding_transcript_variant		5
TM7SF3	ENST00000545344.5 linkuse as main transcript	c.620T>C	p.Met207Thr	missense_variant	6/6	3
TM7SF3	ENST00000544179.1 linkuse as main transcript	n.308T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251214

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Apr 09, 2024

The c.1478T>C (p.M493T) alteration is located in exon 12 (coding exon 12) of the TM7SF3 gene. This alteration results from a T to C substitution at nucleotide position 1478, causing the methionine (M) at amino acid position 493 to be replaced by a threonine (T). 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.17

Sift

Benign

0.042

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.95

P;.

Vest4

0.54

MutPred

0.42

Gain of catalytic residue at W491 (P = 0);.;

MVP

0.31

MPC

0.59

ClinPred

0.84

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.67

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