chr15-50574945-C-T

Variant names:

• chr15-50574945-C-T
• rs16963774
• NM_017672.6:c.4926G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_017672.6(TRPM7):​c.4926G>A​(p.Gly1642Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 1,613,802 control chromosomes in the GnomAD database, including 2,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.080 (808 hom., cov: 32)
  • Exomes 𝑓: 0.044 (2039 hom.)
• Consequence: TRPM7 NM_017672.6 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0480

Genes affected

TRPM7 (HGNC:17994): (transient receptor potential cation channel subfamily M member 7) This gene belongs to the melastatin subfamily of transient receptor potential family of ion channels. The protein encoded by this gene is both an ion channel and a serine/threonine protein kinase. The kinase activity is essential for the ion channel function, which serves to increase intracellular calcium levels and to help regulate magnesium ion homeostasis. The encoded protein is involved in cytoskeletal organization, cell adhesion, cell migration and organogenesis. Defects in this gene are a cause of amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam. The gene may also be associated with defects of cardiac function. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 15-50574945-C-T is Benign according to our data. Variant chr15-50574945-C-T is described in ClinVar as [Benign]. Clinvar id is 3056472.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.048 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.4926G>A	p.Gly1642Gly	synonymous_variant	Exon 34 of 39	ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.4926G>A	p.Gly1642Gly	synonymous_variant	Exon 34 of 39		NM_017672.6	ENSP00000495860.1

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 12179 AN: 152032 Hom.: 808 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0617

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0796

GnomAD2 exomes AF: 0.0484 AC: 12062 AN: 249418 AF XY: 0.0478

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.0386

Gnomad ASJ exome AF: 0.0946

Gnomad EAS exome AF: 0.00206

Gnomad FIN exome AF: 0.0116

Gnomad NFE exome AF: 0.0429

Gnomad OTH exome AF: 0.0507

GnomAD4 exome AF: 0.0439 AC: 64116 AN: 1461652 Hom.: 2039 Cov.: 33 AF XY: 0.0440 AC XY: 32024 AN XY: 727134

Gnomad4 AFR exome AF: 0.191 AC: 6385 AN: 33468

Gnomad4 AMR exome AF: 0.0409 AC: 1828 AN: 44720

Gnomad4 ASJ exome AF: 0.0960 AC: 2509 AN: 26132

Gnomad4 EAS exome AF: 0.000630 AC: 25 AN: 39686

Gnomad4 SAS exome AF: 0.0476 AC: 4109 AN: 86248

Gnomad4 FIN exome AF: 0.0119 AC: 636 AN: 53412

Gnomad4 NFE exome AF: 0.0404 AC: 44881 AN: 1111832

Gnomad4 Remaining exome AF: 0.0533 AC: 3220 AN: 60388

GnomAD4 genome AF: 0.0801 AC: 12188 AN: 152150 Hom.: 808 Cov.: 32 AF XY: 0.0783 AC XY: 5822 AN XY: 74388

Gnomad4 AFR AF: 0.184 AC: 0.183513 AN: 0.183513

Gnomad4 AMR AF: 0.0616 AC: 0.0615757 AN: 0.0615757

Gnomad4 ASJ AF: 0.0899 AC: 0.0899135 AN: 0.0899135

Gnomad4 EAS AF: 0.00309 AC: 0.00308523 AN: 0.00308523

Gnomad4 SAS AF: 0.0439 AC: 0.0439469 AN: 0.0439469

Gnomad4 FIN AF: 0.0135 AC: 0.0134931 AN: 0.0134931

Gnomad4 NFE AF: 0.0404 AC: 0.04038 AN: 0.04038

Gnomad4 OTH AF: 0.0787 AC: 0.0787476 AN: 0.0787476

Alfa AF: 0.0613 Hom.: 1282

Bravo AF: 0.0872

Asia WGS AF: 0.0360 AC: 128 AN: 3478

EpiCase AF: 0.0496

EpiControl AF: 0.0526

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TRPM7-related disorder Benign:1

Dec 11, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	4.5
DANN	Benign	0.65
Mutation Taster		=70/30	polymorphism (auto)

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: rs16963774; hg19: chr15-50867142;