Genetic Variant TMEM151B:p.Ser25Pro (chr6-44270815-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001137560.2(TMEM151B):c.73T>C(p.Ser25Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM151B
NM_001137560.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.360

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047590792).

BP6

Variant 6-44270815-T-C is Benign according to our data. Variant chr6-44270815-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2569564.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM151B	NM_001137560.2 link	c.73T>C	p.Ser25Pro	missense_variant	Exon 1 of 3	ENST00000451188.7	NP_001131032.1	Q8IW70-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM151B	ENST00000451188.7 link	c.73T>C	p.Ser25Pro	missense_variant	Exon 1 of 3	5	NM_001137560.2	ENSP00000393161.2		Q8IW70-1
TMEM151B	ENST00000438774.2 link	c.73T>C	p.Ser25Pro	missense_variant	Exon 1 of 3	3		ENSP00000409337.2		Q8IW70-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

142316

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000511

AC:

AN:

978584

Hom.:

Cov.:

AF XY:

0.00000434

AC XY:

AN XY:

461350

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

0.00000584

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

142316

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69546

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 07, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.0031

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.00058

LIST_S2

Benign

0.19

T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.11

N;N

REVEL

Benign

0.041

Sift

Benign

0.15

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.0

B;B

Vest4

0.045

MutPred

0.17

Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);

MVP

0.040

ClinPred

0.048

GERP RS

3.1

Varity_R

0.12

gMVP

0.21

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over