rs200232307

Variant names:

• chr7-150802272-C-G
• NM_018487.3:c.232C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-150802272-C-G
• chr7-150802272-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018487.3(TMEM176A):​c.232C>G​(p.Arg78Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R78C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM176A NM_018487.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07301158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM176A	NM_018487.3	c.232C>G	p.Arg78Gly	missense_variant	Exon 3 of 7	ENST00000004103.8	NP_060957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM176A	ENST00000004103.8	c.232C>G	p.Arg78Gly	missense_variant	Exon 3 of 7	1	NM_018487.3	ENSP00000004103.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.12
DANN	Benign	0.38
DEOGEN2	Benign	0.0029	T;T;.;T;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.17	.;T;.;T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.073	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.35	N;N;.;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	4.2	N;N;N;N;N
REVEL	Benign	0.047
Sift	Benign	0.75	T;T;T;T;T
Sift4G	Benign	0.56	T;T;T;T;T
Polyphen		0.0	B;B;.;.;.
Vest4		0.21
MutPred		0.64		Loss of stability (P = 0.0969);Loss of stability (P = 0.0969);.;.;.;
MVP		0.13
MPC		0.43
ClinPred		0.021	T
GERP RS		-8.9
Varity_R		0.050
gMVP		0.087

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: chr7-150499360;