Genetic Variant TMEM176B:p.Ser56Tyr (chr7-150796403-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001101312.2(TMEM176B):c.167C>A(p.Ser56Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S56F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TMEM176B
NM_001101312.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Publications

0 publications found

Variant links:

Genes affected

TMEM176B (HGNC:29596): (transmembrane protein 176B) Predicted to be involved in negative regulation of dendritic cell differentiation. Predicted to be located in nuclear membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM176B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36758822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM176B	NM_001101312.2 link	c.167C>A	p.Ser56Tyr	missense_variant	Exon 2 of 7	ENST00000326442.10	NP_001094782.1	Q3YBM2-1A0A090N7V7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM176B	ENST00000326442.10 link	c.167C>A	p.Ser56Tyr	missense_variant	Exon 2 of 7	1	NM_001101312.2	ENSP00000318409.5		Q3YBM2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251228

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000255

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;T;T;T;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.55

.;.;.;T;.;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.37

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M;M;M;M;M

PhyloP100

1.4

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.9

D;D;D;D;D;D

REVEL

Benign

0.046

Sift

Uncertain

0.013

D;D;D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;.

Vest4

0.38

MutPred

0.57

Loss of disorder (P = 0.0301);Loss of disorder (P = 0.0301);Loss of disorder (P = 0.0301);Loss of disorder (P = 0.0301);Loss of disorder (P = 0.0301);Loss of disorder (P = 0.0301);

MVP

0.24

MPC

0.24

ClinPred

0.77

GERP RS

3.2

PromoterAI

-0.028

Neutral

(source)

Varity_R

0.25

gMVP

0.21

Mutation Taster

=95/5

polymorphism

(source)

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

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7-150796403-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over