Variant 2-46480688-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001145051.2(TMEM247):c.401T>C(p.Val134Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,544,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 36)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

TMEM247
NM_001145051.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0470

Variant links:

Genes affected

TMEM247 (HGNC:42967): (transmembrane protein 247) Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TMEM247 links:

TMEM247 (HGNC:):

TMEM247 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010837436).

BP6

Variant 2-46480688-T-C is Benign according to our data. Variant chr2-46480688-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2650874.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM247	NM_001145051.2 linkuse as main transcript	c.401T>C	p.Val134Ala	missense_variant	2/3			A6NEH6
TMEM247	NM_001424184.1 linkuse as main transcript	c.401T>C	p.Val134Ala	missense_variant	2/3		NP_001411113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
TMEM247	ENST00000434431.2 linkuse as main transcript	c.401T>C	p.Val134Ala	missense_variant	2/3	5	ENSP00000388684.1	A6NEH6
ENSG00000284608	ENST00000432241.5 linkuse as main transcript	n.365-3556T>C		intron_variant		3
ENSG00000253515	ENST00000517716.2 linkuse as main transcript	n.80-19043T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000401

AC:

AN:

149556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00121

Gnomad AMR

AF:

0.0000669

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:

0.0000452

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000493

AC:

AN:

152052

Hom.:

AF XY:

0.000458

AC XY:

AN XY:

80874

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.000247

Gnomad ASJ exome

AF:

0.000475

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.000120

Gnomad NFE exome

AF:

0.00100

Gnomad OTH exome

AF:

0.000463

GnomAD4 exome

AF:

0.00122

AC:

1698

AN:

1395006

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

790

AN XY:

688054

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.000365

Gnomad4 ASJ exome

AF:

0.000238

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000632

Gnomad4 FIN exome

AF:

0.000122

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.000881

GnomAD4 genome

AF:

0.0000401

AC:

AN:

149556

Hom.:

Cov.:

AF XY:

0.0000547

AC XY:

AN XY:

73174

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.0000669

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000452

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00902

Hom.:

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00217

AC:

ESP6500EA

AF:

0.00911

AC:

ExAC

AF:

0.000642

AC:

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

Mar 01, 2023

TMEM247: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.39

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

PROVEAN

Benign

-1.1

REVEL

Benign

0.12

Sift

Benign

0.11

Sift4G

Benign

0.26

Polyphen

1.0

MVP

0.055

ClinPred

0.022

GERP RS

0.16

Varity_R

0.042

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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