NM_017636.4:c.1682A>G

Variant names:

• chr19-49183151-A-G
• rs56355369
• NM_017636.4:c.1682A>G

Variant summary

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

The NM_017636.4(TRPM4):​c.1682A>G​(p.Asp561Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D561A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPM4 NM_017636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

Genes affected

TRPM4 (HGNC:17993): (transient receptor potential cation channel subfamily M member 4) The protein encoded by this gene is a calcium-activated nonselective ion channel that mediates transport of monovalent cations across membranes, thereby depolarizing the membrane. The activity of the encoded protein increases with increasing intracellular calcium concentration, but this channel does not transport calcium. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
TRPM4	NM_017636.4	c.1682A>G	p.Asp561Gly	missense_variant	Exon 12 of 25	ENST00000252826.10	NP_060106.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM4	ENST00000252826.10	c.1682A>G	p.Asp561Gly	missense_variant	Exon 12 of 25	1	NM_017636.4	ENSP00000252826.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.84	D;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.86	D;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Uncertain	0.023	D
MutationAssessor	Pathogenic	3.4	M;M
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.012	D;D
Sift4G	Benign	0.076	T;T
Polyphen		0.87	P;D
Vest4		0.42
MutPred		0.56		Gain of MoRF binding (P = 0.0683);Gain of MoRF binding (P = 0.0683);
MVP		0.94
MPC		1.1
ClinPred		0.82	D
GERP RS		4.0
Varity_R		0.55
gMVP		0.64

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

LitVar

Other links and lift over

dbSNP: rs56355369; hg19: chr19-49686408;