2-102814902-A-G

Variant names:

• chr2-102814902-A-G
• rs144729903
• NM_144632.5:c.624A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_144632.5(TMEM182):​c.624A>G​(p.Ile208Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: TMEM182 NM_144632.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.755
• Publications: 1 publications found

Genes affected

TMEM182 (HGNC:26391): (transmembrane protein 182) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14816535).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144632.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM182	NM_144632.5	MANE Select	c.624A>G	p.Ile208Met	missense	Exon 5 of 5	NP_653233.5
	TMEM182	NM_001321343.2		c.495A>G	p.Ile165Met	missense	Exon 7 of 7	NP_001308272.2	B8ZZ71
	TMEM182	NM_001321344.2		c.495A>G	p.Ile165Met	missense	Exon 6 of 6	NP_001308273.2	B8ZZ71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM182	ENST00000412401.3	TSL:1 MANE Select	c.624A>G	p.Ile208Met	missense	Exon 5 of 5	ENSP00000394178.2	Q6ZP80-1
	TMEM182	ENST00000409173.5	TSL:1	c.495A>G	p.Ile165Met	missense	Exon 6 of 6	ENSP00000387184.1	B8ZZ71
	TMEM182	ENST00000409528.5	TSL:1	c.336A>G	p.Ile112Met	missense	Exon 5 of 5	ENSP00000387258.1	Q6ZP80-2

Frequencies

GnomAD3 genomes AF: 0.0000856 AC: 13 AN: 151874 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000147 AC: 37 AN: 251218 AF XY: 0.000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000163 AC: 238 AN: 1461698 Hom.: 0 Cov.: 30 AF XY: 0.000171 AC XY: 124 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53404

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

European-Non Finnish (NFE) AF: 0.000192 AC: 214 AN: 1111950

Other (OTH) AF: 0.000348 AC: 21 AN: 60384

GnomAD4 genome AF: 0.0000856 AC: 13 AN: 151874 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74176

African (AFR) AF: 0.00 AC: 0 AN: 41316

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000193 Hom.: 0

Bravo AF: 0.000102

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000255 AC: 31

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.76
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.21
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.022	D
Polyphen		0.40	B
Vest4		0.35
MVP		0.31
MPC		0.29
ClinPred		0.16	T
GERP RS		-2.9
Varity_R		0.24
gMVP		0.65
Mutation Taster		=84/16	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: rs144729903; hg19: chr2-103431361;