7-150803720-A-G

Position:

• chr7-150803720-A-G

Variant summary

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

The ENST00000004103.8(TMEM176A):​c.443A>G​(p.Asn148Ser) 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. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM176A ENST00000004103.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.32

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM176A	NM_018487.3	c.443A>G	p.Asn148Ser	missense_variant	5/7	ENST00000004103.8	NP_060957.2
TMEM176A	XM_011516376.4	c.494A>G	p.Asn165Ser	missense_variant	5/7		XP_011514678.1
TMEM176A	XM_011516378.3	c.494A>G	p.Asn165Ser	missense_variant	5/6		XP_011514680.1
TMEM176A	XM_024446824.2	c.443A>G	p.Asn148Ser	missense_variant	5/6		XP_024302592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM176A	ENST00000004103.8	c.443A>G	p.Asn148Ser	missense_variant	5/7	1	NM_018487.3	ENSP00000004103.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

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

Feb 05, 2024

The c.443A>G (p.N148S) alteration is located in exon 5 (coding exon 4) of the TMEM176A gene. This alteration results from a A to G substitution at nucleotide position 443, causing the asparagine (N) at amino acid position 148 to be replaced by a serine (S). 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	0.076
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.9
DANN	Benign	0.37
DEOGEN2	Benign	0.0021	T;T;.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Benign	0.39	.;T;.;T;T
M_CAP	Benign	0.00097	T
MetaRNN	Benign	0.066	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.55	N;N;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.59	N;N;N;N;N
REVEL	Benign	0.062
Sift	Benign	0.35	T;T;T;T;T
Sift4G	Benign	0.24	T;T;T;T;T
Polyphen		0.0	B;B;.;.;.
Vest4		0.11
MutPred		0.60		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);.;.;.;
MVP		0.18
MPC		0.27
ClinPred		0.21	T
GERP RS		-1.7
Varity_R		0.031
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.49		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.49		Position offset: 1

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: chr7-150500808;