15-50675526-T-C

Variant names:

• chr15-50675526-T-C
• rs4775899
• NM_017672.6:c.3+11005A>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.3+11005A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,890 control chromosomes in the GnomAD database, including 22,347 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 0.54 (22347 hom., cov: 31)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 6 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)

LOC128092252 (HGNC:0):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.3+11005A>G		intron_variant	Intron 1 of 38	ENST00000646667.1	NP_060142.3
LOC128092252	NM_001414947.1	c.187+11005A>G		intron_variant	Intron 1 of 3	ENST00000676296.1	NP_001401876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.3+11005A>G		intron_variant	Intron 1 of 38		NM_017672.6	ENSP00000495860.1
ENSG00000288645	ENST00000676296.1	c.187+11005A>G		intron_variant	Intron 1 of 3		NM_001414947.1	ENSP00000502268.1
TRPM7	ENST00000560955.5	c.3+11005A>G		intron_variant	Intron 1 of 38	1		ENSP00000453277.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81908 AN: 151772 Hom.: 22341 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.540 AC: 81956 AN: 151890 Hom.: 22347 Cov.: 31 AF XY: 0.540 AC XY: 40105 AN XY: 74232

African (AFR) AF: 0.487 AC: 20151 AN: 41400

American (AMR) AF: 0.617 AC: 9397 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3472

East Asian (EAS) AF: 0.570 AC: 2947 AN: 5166

South Asian (SAS) AF: 0.559 AC: 2697 AN: 4824

European-Finnish (FIN) AF: 0.474 AC: 4987 AN: 10530

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37882 AN: 67944

Other (OTH) AF: 0.586 AC: 1236 AN: 2110

Alfa AF: 0.528 Hom.: 3197

Bravo AF: 0.547

Asia WGS AF: 0.558 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.27
PhyloP100		-1.9
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: rs4775899; hg19: chr15-50967723;