Variant 19-19271072-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000389363.5(TM6SF2):c.149C>T(p.Ala50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,614,146 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 9 hom. )

Consequence

TM6SF2
ENST00000389363.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.40

Variant links:

Genes affected

TM6SF2 (HGNC:11861): (transmembrane 6 superfamily member 2) Enables identical protein binding activity. Involved in regulation of lipid metabolic process. Located in endoplasmic reticulum membrane and endoplasmic reticulum-Golgi intermediate compartment membrane. [provided by Alliance of Genome Resources, Apr 2022]

TM6SF2 links:

TM6SF2 (HGNC:):

TM6SF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061612725).

BP6

Variant 19-19271072-G-A is Benign according to our data. Variant chr19-19271072-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2649605.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TM6SF2	NM_001001524.3 linkuse as main transcript	c.149C>T	p.Ala50Val	missense_variant	2/10	ENST00000389363.5	NP_001001524.2	Q9BZW4-1Q8N8A7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TM6SF2	ENST00000389363.5 linkuse as main transcript	c.149C>T	p.Ala50Val	missense_variant	2/10	1	NM_001001524.3	ENSP00000374014.2		Q9BZW4-1

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

224

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00132

AC:

330

AN:

249506

Hom.:

AF XY:

0.00141

AC XY:

191

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.000371

Gnomad NFE exome

AF:

0.00250

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00253

AC:

3693

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

1776

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.00309

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152272

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00262

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00199

Hom.:

Bravo

AF:

0.00148

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000241

AC:

ESP6500EA

AF:

0.00202

AC:

ExAC

AF:

0.00130

AC:

158

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00213

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

TM6SF2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.58

M_CAP

Benign

0.0052

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.60

REVEL

Benign

0.063

Sift

Benign

0.26

Sift4G

Benign

0.25

Polyphen

0.70

Vest4

0.18

MVP

0.030

MPC

0.33

ClinPred

0.016

GERP RS

3.7

Varity_R

0.035

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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