2-46480487-C-T

Variant summary

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

The NM_001424184.1(TMEM247):​c.200C>T​(p.Pro67Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 1,551,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

TMEM247
NM_001424184.1 missense

Scores

1
3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0380
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=0.020143688).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM247NM_001424184.1 linkc.200C>T p.Pro67Leu missense_variant Exon 2 of 3 NP_001411113.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM247ENST00000434431.2 linkc.200C>T p.Pro67Leu missense_variant Exon 2 of 3 5 ENSP00000388684.1 A6NEH6
ENSG00000284608ENST00000432241.5 linkn.365-3757C>T intron_variant Intron 4 of 4 3
ENSG00000253515ENST00000517716.2 linkn.80-19244C>T intron_variant Intron 2 of 3 5

Frequencies

GnomAD3 genomes
AF:
0.000256
AC:
39
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000358
AC:
56
AN:
156362
Hom.:
0
AF XY:
0.000241
AC XY:
20
AN XY:
82896
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:
0.00167
Gnomad NFE exome
AF:
0.000447
Gnomad OTH exome
AF:
0.000228
GnomAD4 exome
AF:
0.000366
AC:
512
AN:
1399384
Hom.:
0
Cov.:
32
AF XY:
0.000329
AC XY:
227
AN XY:
690194
show subpopulations
Gnomad4 AFR exome
AF:
0.0000316
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00136
Gnomad4 NFE exome
AF:
0.000399
Gnomad4 OTH exome
AF:
0.000224
GnomAD4 genome
AF:
0.000256
AC:
39
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.000310
AC XY:
23
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000943
Gnomad4 NFE
AF:
0.000397
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000278
Hom.:
0
Bravo
AF:
0.000193
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000314
AC:
1
ExAC
AF:
0.000157
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 17, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.200C>T (p.P67L) alteration is located in exon 2 (coding exon 2) of the TMEM247 gene. This alteration results from a C to T substitution at nucleotide position 200, causing the proline (P) at amino acid position 67 to be replaced by a leucine (L). 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
0.10
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
13
DANN
Uncertain
0.98
DEOGEN2
Benign
0.078
T
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.69
T
MetaRNN
Benign
0.020
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.8
L
PROVEAN
Pathogenic
-6.0
D
REVEL
Benign
0.081
Sift
Uncertain
0.010
D
Sift4G
Uncertain
0.020
D
Polyphen
0.086
B
MVP
0.14
ClinPred
0.091
T
GERP RS
2.8
Varity_R
0.056

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.

Other links and lift over

dbSNP: rs376176475; hg19: chr2-46707626; API