Variant 6-44275841-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001137560.2(TMEM151B):c.1015G>A(p.Gly339Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,542,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G339V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

TMEM151B
NM_001137560.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

Variant links:

Genes affected

TMEM151B (HGNC:21315): (transmembrane protein 151B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM151B links:

POLR1C (HGNC:):

POLR1C links:

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=0.012796521).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM151B	NM_001137560.2 linkuse as main transcript	c.1015G>A	p.Gly339Ser	missense_variant	3/3	ENST00000451188.7
POLR1C	NM_001318876.2 linkuse as main transcript	c.946-166049G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM151B	ENST00000451188.7 linkuse as main transcript	c.1015G>A	p.Gly339Ser	missense_variant	3/3	5	NM_001137560.2	P1	Q8IW70-1
TMEM151B	ENST00000438774.2 linkuse as main transcript	c.576+2335G>A		intron_variant		3			Q8IW70-2

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000122

AC:

AN:

139672

Hom.:

AF XY:

0.0000396

AC XY:

AN XY:

75718

show subpopulations

Gnomad AFR exome

AF:

0.00145

Gnomad AMR exome

AF:

0.000286

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000576

AC:

AN:

1389716

Hom.:

Cov.:

AF XY:

0.0000525

AC XY:

AN XY:

685576

show subpopulations

Gnomad4 AFR exome

AF:

0.00181

Gnomad4 AMR exome

AF:

0.000281

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.28e-7

Gnomad4 OTH exome

AF:

0.000173

GnomAD4 genome

AF:

0.000584

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00204

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000204

Hom.:

Bravo

AF:

0.000680

ExAC

AF:

0.0000459

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.1015G>A (p.G339S) alteration is located in exon 3 (coding exon 3) of the TMEM151B gene. This alteration results from a G to A substitution at nucleotide position 1015, causing the glycine (G) at amino acid position 339 to be replaced by a serine (S). 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

0.072

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.0032

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.63

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.56

M_CAP

Benign

0.054

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.4

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.12

REVEL

Benign

0.049

Sift

Benign

0.47

Sift4G

Benign

0.83

Polyphen

0.0

Vest4

0.11

MutPred

0.16

Loss of relative solvent accessibility (P = 0.0186);

MVP

0.030

ClinPred

0.021

GERP RS

2.2

Varity_R

0.053

gMVP

0.30

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