15-50561175-T-C

Variant names:

• chr15-50561175-T-C
• rs11070795
• NM_017672.6:c.*503A>G

Variant summary

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

The NM_017672.6(TRPM7):​c.*503A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,864 control chromosomes in the GnomAD database, including 9,119 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 0.33 (9062 hom., cov: 31)
  • Exomes 𝑓: 0.39 (57 hom.)
• Consequence: TRPM7 NM_017672.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.*503A>G		3_prime_UTR_variant	Exon 39 of 39	ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.*503A>G		3_prime_UTR_variant	Exon 39 of 39		NM_017672.6	ENSP00000495860.1
TRPM7	ENST00000560955.5	c.*503A>G		3_prime_UTR_variant	Exon 39 of 39	1		ENSP00000453277.1
TRPM7	ENST00000561267.5	c.605-8478A>G		intron_variant	Intron 5 of 5	3		ENSP00000454066.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49852 AN: 151890 Hom.: 9063 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.386 AC: 330 AN: 854 Hom.: 57 Cov.: 0 AF XY: 0.404 AC XY: 205 AN XY: 508

African (AFR) AF: 0.375 AC: 6 AN: 16

American (AMR) AF: 0.500 AC: 4 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 4 AN: 22

East Asian (EAS) AF: 0.313 AC: 10 AN: 32

South Asian (SAS) AF: 0.375 AC: 3 AN: 8

European-Finnish (FIN) AF: 0.400 AC: 144 AN: 360

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.390 AC: 146 AN: 374

Other (OTH) AF: 0.382 AC: 13 AN: 34

GnomAD4 genome AF: 0.328 AC: 49867 AN: 152010 Hom.: 9062 Cov.: 31 AF XY: 0.329 AC XY: 24424 AN XY: 74284

African (AFR) AF: 0.173 AC: 7178 AN: 41496

American (AMR) AF: 0.327 AC: 4993 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1417 AN: 3470

East Asian (EAS) AF: 0.354 AC: 1825 AN: 5162

South Asian (SAS) AF: 0.428 AC: 2063 AN: 4818

European-Finnish (FIN) AF: 0.421 AC: 4433 AN: 10528

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.395 AC: 26865 AN: 67964

Other (OTH) AF: 0.339 AC: 713 AN: 2106

Alfa AF: 0.367 Hom.: 13451

Bravo AF: 0.313

Asia WGS AF: 0.368 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.098
DANN	Benign	0.58
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs11070795; hg19: chr15-50853372;