15-50600917-G-T

Position:

• chr15-50600917-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017672.6(TRPM7):​c.2989-1621C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,108 control chromosomes in the GnomAD database, including 2,219 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2219 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.2989-1621C>A		intron_variant		ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.2989-1621C>A		intron_variant			NM_017672.6	ENSP00000495860.1
TRPM7	ENST00000560955.5	c.2989-1621C>A		intron_variant		1		ENSP00000453277.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22368 AN: 151990 Hom.: 2220 Cov.: 32

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.147 AC: 22373 AN: 152108 Hom.: 2219 Cov.: 32 AF XY: 0.147 AC XY: 10966 AN XY: 74352

Gnomad4 AFR AF: 0.0435

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.184

Alfa AF: 0.0603 Hom.: 67

Bravo AF: 0.155

Asia WGS AF: 0.0890 AC: 308 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.040
DANN	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4775892; hg19: chr15-50893114;