1-15219737-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001136218.2(TMEM51):​c.756C>T​(p.Pro252Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000804 in 1,612,574 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 7 hom., cov: 32)
Exomes 𝑓: 0.00066 ( 11 hom. )

Consequence

TMEM51
NM_001136218.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.52
Variant links:
Genes affected
TMEM51 (HGNC:25488): (transmembrane protein 51) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 1-15219737-C-T is Benign according to our data. Variant chr1-15219737-C-T is described in ClinVar as [Benign]. Clinvar id is 731484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.52 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00219 (334/152334) while in subpopulation AMR AF= 0.0205 (314/15302). AF 95% confidence interval is 0.0187. There are 7 homozygotes in gnomad4. There are 208 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM51NM_001136218.2 linkc.756C>T p.Pro252Pro synonymous_variant Exon 4 of 4 ENST00000376008.3 NP_001129690.1 Q9NW97A0A024QZ97

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM51ENST00000376008.3 linkc.756C>T p.Pro252Pro synonymous_variant Exon 4 of 4 2 NM_001136218.2 ENSP00000365176.1 Q9NW97

Frequencies

GnomAD3 genomes
AF:
0.00219
AC:
333
AN:
152216
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0205
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00115
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.00267
AC:
658
AN:
246452
Hom.:
7
AF XY:
0.00225
AC XY:
303
AN XY:
134398
show subpopulations
Gnomad AFR exome
AF:
0.000132
Gnomad AMR exome
AF:
0.0170
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00234
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000989
Gnomad OTH exome
AF:
0.00234
GnomAD4 exome
AF:
0.000659
AC:
963
AN:
1460240
Hom.:
11
Cov.:
32
AF XY:
0.000613
AC XY:
445
AN XY:
726250
show subpopulations
Gnomad4 AFR exome
AF:
0.000180
Gnomad4 AMR exome
AF:
0.0174
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00171
Gnomad4 SAS exome
AF:
0.000255
Gnomad4 FIN exome
AF:
0.0000568
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.000580
GnomAD4 genome
AF:
0.00219
AC:
334
AN:
152334
Hom.:
7
Cov.:
32
AF XY:
0.00279
AC XY:
208
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.0205
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000357
Hom.:
0
Bravo
AF:
0.00269
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
May 29, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
0.12
DANN
Benign
0.57

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: rs138490339; hg19: chr1-15546233; API