rs10519282

Variant names:

• chr15-50602931-C-T
• rs10519282
• NM_017672.6:c.2988+1935G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_017672.6(TRPM7):​c.2988+1935G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 152,248 control chromosomes in the GnomAD database, including 103 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 0.031 (103 hom., cov: 31)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hypomagnesemia, seizures, and intellectual disability

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• autosomal dominant macrothrombocytopenia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• macrothrombocytopenia, isolated

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• amyotrophic lateral sclerosis-parkinsonism-dementia complex

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0313 (4764/152248) while in subpopulation AMR AF = 0.0459 (701/15286). AF 95% confidence interval is 0.043. There are 103 homozygotes in GnomAd4. There are 2321 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4764 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.2988+1935G>A		intron_variant	Intron 21 of 38	ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.2988+1935G>A		intron_variant	Intron 21 of 38		NM_017672.6	ENSP00000495860.1
TRPM7	ENST00000560955.5	c.2988+1935G>A		intron_variant	Intron 21 of 38	1		ENSP00000453277.1

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4767 AN: 152130 Hom.: 104 Cov.: 31

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0460

Gnomad ASJ AF: 0.0831

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0459

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

GnomAD4 genome AF: 0.0313 AC: 4764 AN: 152248 Hom.: 103 Cov.: 31 AF XY: 0.0312 AC XY: 2321 AN XY: 74442

African (AFR) AF: 0.0134 AC: 555 AN: 41556

American (AMR) AF: 0.0459 AC: 701 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0831 AC: 288 AN: 3464

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5190

South Asian (SAS) AF: 0.0431 AC: 208 AN: 4822

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10610

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0400 AC: 2719 AN: 68000

Other (OTH) AF: 0.0454 AC: 96 AN: 2114

Alfa AF: 0.0361 Hom.: 53

Bravo AF: 0.0320

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10519282; hg19: chr15-50895128;