rs3131583

Variant names:

• chr15-50556799-A-G
• rs3131583
• ENST00000561267.5:c.605-4102T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000561267.5(TRPM7):​c.605-4102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,206 control chromosomes in the GnomAD database, including 3,322 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 0.18 (3322 hom., cov: 33)
• Consequence: TRPM7 ENST00000561267.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000561267.5	c.605-4102T>C		intron_variant	Intron 5 of 5	3		ENSP00000454066.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27977 AN: 152086 Hom.: 3325 Cov.: 33

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.184 AC: 27973 AN: 152206 Hom.: 3322 Cov.: 33 AF XY: 0.191 AC XY: 14215 AN XY: 74424

African (AFR) AF: 0.0467 AC: 1943 AN: 41570

American (AMR) AF: 0.193 AC: 2953 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3470

East Asian (EAS) AF: 0.464 AC: 2393 AN: 5160

South Asian (SAS) AF: 0.247 AC: 1192 AN: 4824

European-Finnish (FIN) AF: 0.276 AC: 2920 AN: 10590

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15172 AN: 67984

Other (OTH) AF: 0.207 AC: 437 AN: 2116

Alfa AF: 0.208 Hom.: 11361

Bravo AF: 0.173

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.2
DANN	Benign	0.72
PhyloP100		0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3131583; hg19: chr15-50848996;