rs12905120

Positions:

• chr15-50642146-T-C

Variant summary

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

The NM_017672.6(TRPM7):​c.535+1194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,156 control chromosomes in the GnomAD database, including 571 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 0.078 (571 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.535+1194A>G		intron_variant		ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.535+1194A>G		intron_variant			NM_017672.6	ENSP00000495860	A1
TRPM7	ENST00000560955.5	c.535+1194A>G		intron_variant		1		ENSP00000453277	P4

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11809 AN: 152038 Hom.: 569 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.0987

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0780

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

GnomAD4 genome AF: 0.0777 AC: 11822 AN: 152156 Hom.: 571 Cov.: 32 AF XY: 0.0761 AC XY: 5665 AN XY: 74414

Gnomad4 AFR AF: 0.0304

Gnomad4 AMR AF: 0.0653

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.0983

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0530

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0824

Alfa AF: 0.0861 Hom.: 69

Bravo AF: 0.0737

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.038
DANN	Benign	0.21

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: rs12905120; hg19: chr15-50934343;