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

Variant summary

Our verdict is Uncertain significance. The variant received 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

Publications

0 publications found

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:

LINC02583 (HGNC:53812): (long intergenic non-protein coding RNA 2583)

LINC02583 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424184.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM247	NM_001424184.1	MANE Select	c.328C>G	p.Arg110Gly	missense	Exon 2 of 3	NP_001411113.1	A6NEH6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM247	ENST00000434431.2	TSL:5 MANE Select	c.328C>G	p.Arg110Gly	missense	Exon 2 of 3	ENSP00000388684.1	A6NEH6
ENSG00000284608	ENST00000432241.5	TSL:3	n.365-3629C>G		intron	N/A
ENSG00000253515	ENST00000517716.3	TSL:5	n.114-19116C>G		intron	N/A

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

GnomAD2 exomes

AF:

0.00000643

AC:

AN:

155480

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

30740

American (AMR)

AF:

0.00

AC:

AN:

33252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23126

East Asian (EAS)

AF:

0.00

AC:

AN:

27786

South Asian (SAS)

AF:

0.0000508

AC:

AN:

78682

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5394

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1041856

Other (OTH)

AF:

0.00

AC:

AN:

54134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000837

AC:

AN:

119404

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

57512

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

35274

American (AMR)

AF:

0.00

AC:

AN:

10674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2766

East Asian (EAS)

AF:

0.00

AC:

AN:

3272

South Asian (SAS)

AF:

0.000280

AC:

AN:

3568

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

222

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53782

Other (OTH)

AF:

0.00

AC:

AN:

1598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.0000372

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

(source)

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

PhyloP100

0.33

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over