chr7-150801642-A-G

Position:

• chr7-150801642-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000004103.8(TMEM176A):​c.92A>G​(p.Lys31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: TMEM176A ENST00000004103.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

Genes affected

TMEM176A (HGNC:24930): (transmembrane protein 176A) Predicted to be involved in negative regulation of dendritic cell differentiation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM176A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29817906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM176A	NM_018487.3	c.92A>G	p.Lys31Arg	missense_variant	2/7	ENST00000004103.8	NP_060957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM176A	ENST00000004103.8	c.92A>G	p.Lys31Arg	missense_variant	2/7	1	NM_018487.3	ENSP00000004103.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.92A>G (p.K31R) alteration is located in exon 2 (coding exon 1) of the TMEM176A gene. This alteration results from a A to G substitution at nucleotide position 92, causing the lysine (K) at amino acid position 31 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;T
Eigen	Benign	-0.016
Eigen_PC	Benign	-0.014
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.094
Sift	Benign	0.11	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.82	P;P
Vest4		0.27
MutPred		0.69		Loss of ubiquitination at K31 (P = 0.0155);Loss of ubiquitination at K31 (P = 0.0155);
MVP		0.36
MPC		0.79
ClinPred		0.95	D
GERP RS		3.8
Varity_R		0.18
gMVP		0.20

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.

Other links and lift over

hg19: chr7-150498730;