Genetic Variant TMEM247:p.Arg110Gly (chr2-46480615-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001424184.1(TMEM247):c.328C>G(p.Arg110Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R110C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000084 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

TMEM247
NM_001424184.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.330

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:

ENSG00000284608 (HGNC:):

ENSG00000284608 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3284131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM247	NM_001424184.1 link	c.328C>G	p.Arg110Gly	missense_variant	Exon 2 of 3		NP_001411113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
TMEM247	ENST00000434431.2 link	c.328C>G	p.Arg110Gly	missense_variant	Exon 2 of 3	5	ENSP00000388684.1	A6NEH6
ENSG00000284608	ENST00000432241.5 link	n.365-3629C>G		intron_variant	Intron 4 of 4	3
ENSG00000253515	ENST00000517716.2 link	n.80-19116C>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.00000838

AC:

AN:

119284

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000281

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000643

AC:

AN:

155480

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82506

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:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000299

AC:

AN:

1338870

Hom.:

Cov.:

AF XY:

0.00000455

AC XY:

AN XY:

659330

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:

0.0000508

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000837

AC:

AN:

119404

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

57512

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000280

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000372

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

0.097

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.74

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.4

PROVEAN

Pathogenic

-6.3

REVEL

Uncertain

0.54

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.013

Polyphen

0.86

MutPred

0.19

Loss of helix (P = 0.0068);

MVP

0.22

ClinPred

0.94

GERP RS

2.7

Varity_R

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over