rs17256042

Variant names:

• chr7-150793150-G-A
• rs17256042
• NM_001101312.2:c.538C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001101312.2(TMEM176B):​c.538C>T​(p.Arg180Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 1,614,104 control chromosomes in the GnomAD database, including 1,673 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.033 (102 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1571 hom.)
• Consequence: TMEM176B NM_001101312.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 17 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002884835).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101312.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM176B	NM_001101312.2	MANE Select	c.538C>T	p.Arg180Trp	missense	Exon 5 of 7	NP_001094782.1
	TMEM176B	NM_001362691.2		c.586C>T	p.Arg196Trp	missense	Exon 7 of 9	NP_001349620.1
	TMEM176B	NM_001362692.2		c.586C>T	p.Arg196Trp	missense	Exon 6 of 8	NP_001349621.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM176B	ENST00000326442.10	TSL:1 MANE Select	c.538C>T	p.Arg180Trp	missense	Exon 5 of 7	ENSP00000318409.5
	TMEM176B	ENST00000447204.6	TSL:1	c.538C>T	p.Arg180Trp	missense	Exon 5 of 7	ENSP00000410269.2
	TMEM176B	ENST00000429904.6	TSL:2	c.538C>T	p.Arg180Trp	missense	Exon 4 of 6	ENSP00000397810.2

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5038 AN: 152140 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0325

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.00828

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0505

Gnomad OTH AF: 0.0301

GnomAD2 exomes AF: 0.0330 AC: 8294 AN: 251370 AF XY: 0.0328

Gnomad AFR exome AF: 0.0102

Gnomad AMR exome AF: 0.0224

Gnomad ASJ exome AF: 0.0405

Gnomad EAS exome AF: 0.00217

Gnomad FIN exome AF: 0.0306

Gnomad NFE exome AF: 0.0500

Gnomad OTH exome AF: 0.0373

GnomAD4 exome AF: 0.0436 AC: 63718 AN: 1461846 Hom.: 1571 Cov.: 32 AF XY: 0.0430 AC XY: 31259 AN XY: 727222

African (AFR) AF: 0.0100 AC: 335 AN: 33480

American (AMR) AF: 0.0226 AC: 1013 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0391 AC: 1023 AN: 26136

East Asian (EAS) AF: 0.00116 AC: 46 AN: 39700

South Asian (SAS) AF: 0.0104 AC: 901 AN: 86252

European-Finnish (FIN) AF: 0.0313 AC: 1673 AN: 53414

Middle Eastern (MID) AF: 0.0520 AC: 300 AN: 5768

European-Non Finnish (NFE) AF: 0.0504 AC: 56066 AN: 1111976

Other (OTH) AF: 0.0391 AC: 2361 AN: 60396

GnomAD4 genome AF: 0.0331 AC: 5033 AN: 152258 Hom.: 102 Cov.: 32 AF XY: 0.0318 AC XY: 2368 AN XY: 74432

African (AFR) AF: 0.0111 AC: 460 AN: 41536

American (AMR) AF: 0.0325 AC: 497 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5176

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4826

European-Finnish (FIN) AF: 0.0290 AC: 308 AN: 10612

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0505 AC: 3434 AN: 68016

Other (OTH) AF: 0.0293 AC: 62 AN: 2114

Alfa AF: 0.0442 Hom.: 595

Bravo AF: 0.0321

TwinsUK AF: 0.0518 AC: 192

ALSPAC AF: 0.0509 AC: 196

ESP6500AA AF: 0.00999 AC: 44

ESP6500EA AF: 0.0533 AC: 458

ExAC AF: 0.0329 AC: 3996

Asia WGS AF: 0.00664 AC: 24 AN: 3478

EpiCase AF: 0.0500

EpiControl AF: 0.0522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.23
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.082
Sift	Benign	0.073	T
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.14
MPC		0.19
ClinPred		0.022	T
GERP RS		-2.4
Varity_R		0.049
gMVP		0.18
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs17256042; hg19: chr7-150490238;