chr7-150793102-T-C

Variant names:

• chr7-150793102-T-C
• rs750841048
• NM_001101312.2:c.586A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001101312.2(TMEM176B):​c.586A>G​(p.Met196Val) 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 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. 15/22 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. M196L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM176B NM_001101312.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM176B	NM_001101312.2	c.586A>G	p.Met196Val	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.586A>G	p.Met196Val	missense_variant	Exon 5 of 7	1	NM_001101312.2	ENSP00000318409.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461780 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727178

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111948

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.84
DEOGEN2	Benign	0.087	T;T;T;T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.60	.;.;.;T;.;T
M_CAP	Benign	0.0040	T
MetaRNN	Uncertain	0.67	D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;L;L;L;.
PhyloP100		1.8
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.3	N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.11	T;T;T;T;T;T
Sift4G	Uncertain	0.037	D;D;D;D;D;D
Polyphen		0.95	P;P;P;P;P;.
Vest4		0.49
MutPred		0.66		Loss of MoRF binding (P = 0.1075);Loss of MoRF binding (P = 0.1075);Loss of MoRF binding (P = 0.1075);Loss of MoRF binding (P = 0.1075);Loss of MoRF binding (P = 0.1075);.;
MVP		0.11
MPC		0.19
ClinPred		0.39	T
GERP RS		2.5
Varity_R		0.068
gMVP		0.30
Mutation Taster		=97/3	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: rs750841048; hg19: chr7-150490190;