chr15-50561374-A-G

Position:

• chr15-50561374-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017672.6(TRPM7):​c.*304T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 245,276 control chromosomes in the GnomAD database, including 38,442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23511 hom., cov: 32)
  • Exomes 𝑓: 0.56 (14931 hom.)
• Consequence: TRPM7 NM_017672.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.433

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]

TRPM7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 15-50561374-A-G is Benign according to our data. Variant chr15-50561374-A-G is described in ClinVar as [Benign]. Clinvar id is 1281710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.*304T>C		3_prime_UTR_variant	39/39	ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667	c.*304T>C		3_prime_UTR_variant	39/39		NM_017672.6	ENSP00000495860.1
TRPM7	ENST00000560955	c.*304T>C		3_prime_UTR_variant	39/39	1		ENSP00000453277.1
TRPM7	ENST00000561267.5	c.604+8513T>C		intron_variant		3		ENSP00000454066.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84223 AN: 151894 Hom.: 23494 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.561 AC: 52296 AN: 93260 Hom.: 14931 Cov.: 2 AF XY: 0.562 AC XY: 26874 AN XY: 47822

Gnomad4 AFR exome AF: 0.541

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.568

Gnomad4 EAS exome AF: 0.571

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.554 AC: 84291 AN: 152016 Hom.: 23511 Cov.: 32 AF XY: 0.555 AC XY: 41209 AN XY: 74300

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.591

Alfa AF: 0.565 Hom.: 41111

Bravo AF: 0.565

Asia WGS AF: 0.554 AC: 1925 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs616256; hg19: chr15-50853571;