7-150793301-G-T

Variant names:

• chr7-150793301-G-T
• rs745707041
• NM_001101312.2:c.387C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001101312.2(TMEM176B):​c.387C>A​(p.Ser129Arg) 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. 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: 32)
• Consequence: TMEM176B NM_001101312.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.75
• Publications: 0 publications found

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]

ACMG classification

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=0.31032008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM176B	NM_001101312.2	c.387C>A	p.Ser129Arg	missense_variant	Exon 5 of 7	ENST00000326442.10	NP_001094782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM176B	ENST00000326442.10	c.387C>A	p.Ser129Arg	missense_variant	Exon 5 of 7	1	NM_001101312.2	ENSP00000318409.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.387C>A (p.S129R) alteration is located in exon 5 (coding exon 4) of the TMEM176B gene. This alteration results from a C to A substitution at nucleotide position 387, causing the serine (S) at amino acid position 129 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.064
DANN	Benign	0.76
DEOGEN2	Benign	0.042	T;T;T;T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.47	.;.;.;T;.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.31	T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N;N;N;N;N;.
PhyloP100		-1.8
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N
REVEL	Benign	0.087
Sift	Benign	0.088	T;T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;.
Vest4		0.25
MutPred		0.39		Gain of methylation at S129 (P = 0.05);Gain of methylation at S129 (P = 0.05);Gain of methylation at S129 (P = 0.05);Gain of methylation at S129 (P = 0.05);Gain of methylation at S129 (P = 0.05);.;
MVP		0.13
MPC		0.043
ClinPred		0.12	T
GERP RS		-8.6
Varity_R		0.20
gMVP		0.50
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs745707041; hg19: chr7-150490389;