rs141997826

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001321282.2(TRPM4):c.-684C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,613,980 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0037 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 15 hom. )

Consequence

TRPM4
NM_001321282.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:7

Conservation

PhyloP100: -2.22

Variant links:

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]

TRPM4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 19-49171589-C-T is Benign according to our data. Variant chr19-49171589-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 386319.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=3, Uncertain_significance=1}. Variant chr19-49171589-C-T is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 560 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM4	NM_017636.4 link	c.870C>T	p.Asn290Asn	synonymous_variant	Exon 8 of 25	ENST00000252826.10	NP_060106.2	Q8TD43-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM4	ENST00000252826.10 link	c.870C>T	p.Asn290Asn	synonymous_variant	Exon 8 of 25	1	NM_017636.4	ENSP00000252826.4		Q8TD43-1

Frequencies

GnomAD3 genomes

AF:

0.00368

AC:

560

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00680

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00543

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00313

AC:

785

AN:

250494

Hom.:

AF XY:

0.00327

AC XY:

444

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.000376

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00249

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00693

Gnomad NFE exome

AF:

0.00466

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00391

AC:

5714

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

2748

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00214

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00743

Gnomad4 NFE exome

AF:

0.00445

Gnomad4 OTH exome

AF:

0.00359

GnomAD4 genome

AF:

0.00368

AC:

560

AN:

152192

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

271

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.00236

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00680

Gnomad4 NFE

AF:

0.00544

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00451

Hom.:

Bravo

AF:

0.00328

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00409

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:7

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TRPM4: BP4, BP7, BS2 -

Nov 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Progressive familial heart block type IB

Uncertain:1Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Aug 27, 2015

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.1

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over