chr2-102764396-G-T

Variant names:

• chr2-102764396-G-T
• NM_144632.5:c.300G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144632.5(TMEM182):​c.300G>T​(p.Glu100Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,610 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TMEM182 NM_144632.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0530
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0662128).

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.300G>T	p.Glu100Asp	missense	Exon 3 of 5	NP_653233.5
	TMEM182	NM_001321343.2		c.171G>T	p.Glu57Asp	missense	Exon 5 of 7	NP_001308272.2	B8ZZ71
	TMEM182	NM_001321344.2		c.171G>T	p.Glu57Asp	missense	Exon 4 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.300G>T	p.Glu100Asp	missense	Exon 3 of 5	ENSP00000394178.2	Q6ZP80-1
	TMEM182	ENST00000409173.5	TSL:1	c.171G>T	p.Glu57Asp	missense	Exon 4 of 6	ENSP00000387184.1	B8ZZ71
	TMEM182	ENST00000409528.5	TSL:1	c.12G>T	p.Glu4Asp	missense	Exon 3 of 5	ENSP00000387258.1	Q6ZP80-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461610 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727130

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111854

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		-0.053
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.026
Sift	Benign	0.50	T
Sift4G	Benign	0.64	T
Polyphen		0.26	B
Vest4		0.35
MutPred		0.12		Gain of catalytic residue at G99 (P = 0.1746)
MVP		0.092
MPC		0.11
ClinPred		0.25	T
GERP RS		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.073
gMVP		0.61
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr2-103380855;