Variant 2-46479620-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001145051.2(TMEM247):c.35G>A(p.Arg12Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000999 in 1,551,588 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 3 hom. )

Consequence

TMEM247
NM_001145051.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.847

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020582616).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM247	NM_001145051.2 linkuse as main transcript	c.35G>A	p.Arg12Gln	missense_variant	1/3			A6NEH6
TMEM247	NM_001424184.1 linkuse as main transcript	c.35G>A	p.Arg12Gln	missense_variant	1/3		NP_001411113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
TMEM247	ENST00000434431.2 linkuse as main transcript	c.35G>A	p.Arg12Gln	missense_variant	1/3	5	ENSP00000388684.1	A6NEH6
ENSG00000284608	ENST00000432241.5 linkuse as main transcript	n.365-4624G>A		intron_variant		3
ENSG00000253515	ENST00000517716.2 linkuse as main transcript	n.80-20111G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000223

AC:

AN:

156606

Hom.:

AF XY:

0.000301

AC XY:

AN XY:

82978

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000284

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00123

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000107

AC:

150

AN:

1399406

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

104

AN XY:

690206

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000241

Gnomad4 OTH exome

AF:

0.0000862

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000557

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000422

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

Dec 21, 2023

The c.35G>A (p.R12Q) alteration is located in exon 1 (coding exon 1) of the TMEM247 gene. This alteration results from a G to A substitution at nucleotide position 35, causing the arginine (R) at amino acid position 12 to be replaced by a glutamine (Q). 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

0.098

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0089

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.68

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.026

Sift

Benign

0.041

Sift4G

Benign

0.19

Polyphen

0.086

MutPred

0.17

Gain of catalytic residue at R12 (P = 0.0372);

MVP

0.040

ClinPred

0.10

GERP RS

2.2

Varity_R

0.055

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