Variant 6-44273126-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001137560.2(TMEM151B):c.196C>T(p.Leu66Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000068 in 1,529,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

TMEM151B
NM_001137560.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM151B	NM_001137560.2 linkuse as main transcript	c.196C>T	p.Leu66Phe	missense_variant	2/3	ENST00000451188.7
POLR1C	NM_001318876.2 linkuse as main transcript	c.946-168764C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM151B	ENST00000451188.7 linkuse as main transcript	c.196C>T	p.Leu66Phe	missense_variant	2/3	5	NM_001137560.2	P1	Q8IW70-1
TMEM151B	ENST00000438774.2 linkuse as main transcript	c.196C>T	p.Leu66Phe	missense_variant	2/3	3			Q8IW70-2

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152228

Hom.:

Cov.:

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000476

AC:

AN:

147196

Hom.:

AF XY:

0.0000519

AC XY:

AN XY:

77134

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.000132

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000653

AC:

AN:

1377574

Hom.:

Cov.:

AF XY:

0.0000548

AC XY:

AN XY:

675668

show subpopulations

Gnomad4 AFR exome

AF:

0.0000319

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:

0.000106

Gnomad4 NFE exome

AF:

0.0000780

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74370

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:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000660

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000259

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

Mar 14, 2023

The c.196C>T (p.L66F) alteration is located in exon 2 (coding exon 2) of the TMEM151B gene. This alteration results from a C to T substitution at nucleotide position 196, causing the leucine (L) at amino acid position 66 to be replaced by a phenylalanine (F). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Uncertain

-0.070

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.18

T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

T;D

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.3

D;D

REVEL

Uncertain

0.43

Sift

Benign

0.065

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.70

MVP

0.092

ClinPred

0.58

GERP RS

4.1

Varity_R

0.42

gMVP

0.84

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.

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