2-46479657-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145051.2(TMEM247):​c.72G>T​(p.Met24Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000754 in 1,551,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

TMEM247
NM_001145051.2 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.041681796).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM247NM_001145051.2 linkuse as main transcriptc.72G>T p.Met24Ile missense_variant 1/3 A6NEH6
TMEM247NM_001424184.1 linkuse as main transcriptc.72G>T p.Met24Ile missense_variant 1/3 NP_001411113.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM247ENST00000434431.2 linkuse as main transcriptc.72G>T p.Met24Ile missense_variant 1/35 ENSP00000388684.1 A6NEH6
ENSG00000284608ENST00000432241.5 linkuse as main transcriptn.365-4587G>T intron_variant 3
ENSG00000253515ENST00000517716.2 linkuse as main transcriptn.80-20074G>T intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000255
AC:
4
AN:
156816
Hom.:
0
AF XY:
0.0000361
AC XY:
3
AN XY:
83062
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000658
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000757
AC:
106
AN:
1399442
Hom.:
0
Cov.:
30
AF XY:
0.0000753
AC XY:
52
AN XY:
690232
show subpopulations
Gnomad4 AFR exome
AF:
0.0000316
Gnomad4 AMR exome
AF:
0.0000280
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000936
Gnomad4 OTH exome
AF:
0.0000345
GnomAD4 genome
AF:
0.0000722
AC:
11
AN:
152306
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.0000384
AC:
1

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 submitterclinical testingAmbry GeneticsOct 06, 2021The c.72G>T (p.M24I) alteration is located in exon 1 (coding exon 1) of the TMEM247 gene. This alteration results from a G to T substitution at nucleotide position 72, causing the methionine (M) at amino acid position 24 to be replaced by an isoleucine (I). 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
0.28
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
16
DANN
Benign
0.92
DEOGEN2
Benign
0.0058
T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.60
T
MetaRNN
Benign
0.042
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.8
L
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.040
Sift
Benign
0.41
T
Sift4G
Benign
0.38
T
Polyphen
0.013
B
MutPred
0.096
Gain of catalytic residue at P26 (P = 0.0305);
MVP
0.030
ClinPred
0.039
T
GERP RS
4.1
Varity_R
0.30

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.

Other links and lift over

dbSNP: rs765642084; hg19: chr2-46706796; API