Variant 1-15215144-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001136218.2(TMEM51):c.57G>A(p.Leu19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00847 in 1,614,124 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0087 ( 66 hom. )

Consequence

TMEM51
NM_001136218.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.23

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]

TMEM51 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 1-15215144-G-A is Benign according to our data. Variant chr1-15215144-G-A is described in ClinVar as [Benign]. Clinvar id is 771685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.23 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM51	NM_001136218.2 linkuse as main transcript	c.57G>A	p.Leu19=	synonymous_variant	3/4	ENST00000376008.3	NP_001129690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM51	ENST00000376008.3 linkuse as main transcript	c.57G>A	p.Leu19=	synonymous_variant	3/4	2	NM_001136218.2	ENSP00000365176	P1

Frequencies

GnomAD3 genomes

AF:

0.00611

AC:

930

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00607

AC:

1525

AN:

251202

Hom.:

AF XY:

0.00617

AC XY:

838

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00510

Gnomad FIN exome

AF:

0.00353

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.00871

AC:

12736

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00873

AC XY:

6348

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.00666

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00464

Gnomad4 FIN exome

AF:

0.00405

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.00864

GnomAD4 genome

AF:

0.00609

AC:

928

AN:

152362

Hom.:

Cov.:

AF XY:

0.00597

AC XY:

445

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00498

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00875

Hom.:

Bravo

AF:

0.00580

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00960

EpiControl

AF:

0.00812

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.4

DANN

Benign

0.78

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over