Genetic Variant NM_001101312.2:c.5C>T (chr7-150796565-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001101312.2(TMEM176B):c.5C>T(p.Thr2Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TMEM176B
NM_001101312.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.530

Publications

6 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17029342).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101312.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM176B	NM_001101312.2	MANE Select	c.5C>T	p.Thr2Met	missense	Exon 2 of 7	NP_001094782.1	Q3YBM2-1
TMEM176B	NM_001362691.2		c.53C>T	p.Thr18Met	missense	Exon 4 of 9	NP_001349620.1
TMEM176B	NM_001362692.2		c.53C>T	p.Thr18Met	missense	Exon 3 of 8	NP_001349621.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM176B	ENST00000326442.10	TSL:1 MANE Select	c.5C>T	p.Thr2Met	missense	Exon 2 of 7	ENSP00000318409.5	Q3YBM2-1
TMEM176B	ENST00000447204.6	TSL:1	c.5C>T	p.Thr2Met	missense	Exon 2 of 7	ENSP00000410269.2	Q3YBM2-1
TMEM176B	ENST00000854817.1		c.5C>T	p.Thr2Met	missense	Exon 2 of 9	ENSP00000524876.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251380

AF XY:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461466

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727022

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33476

American (AMR)

AF:

0.0000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111994

Other (OTH)

AF:

0.0000166

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.55

M_CAP

Benign

0.0065

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.53

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.2

REVEL

Benign

0.042

Sift

Benign

0.042

Sift4G

Uncertain

0.031

Polyphen

0.99

Vest4

0.17

MutPred

0.24

Loss of catalytic residue at T2 (P = 0.0205)

MVP

0.11

MPC

0.22

ClinPred

0.95

GERP RS

2.7

PromoterAI

-0.069

Neutral

(source)

Varity_R

0.026

gMVP

0.43

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over