NM_017672.6:c.83+2494A>G

Variant names:

• chr15-50660473-T-C
• rs11854486
• NM_017672.6:c.83+2494A>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.83+2494A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 152,138 control chromosomes in the GnomAD database, including 557 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 0.075 (557 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851
• Publications: 2 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)

ENSG00000288645 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.83+2494A>G		intron_variant	Intron 2 of 38	ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.83+2494A>G		intron_variant	Intron 2 of 38		NM_017672.6	ENSP00000495860.1
TRPM7	ENST00000560955.5	c.83+2494A>G		intron_variant	Intron 2 of 38	1		ENSP00000453277.1
ENSG00000288645	ENST00000676296.1	c.267+2494A>G		intron_variant	Intron 2 of 3			ENSP00000502268.1

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 11452 AN: 152020 Hom.: 555 Cov.: 32

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0529

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0747

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

GnomAD4 genome AF: 0.0753 AC: 11459 AN: 152138 Hom.: 557 Cov.: 32 AF XY: 0.0738 AC XY: 5488 AN XY: 74386

African (AFR) AF: 0.0218 AC: 906 AN: 41526

American (AMR) AF: 0.0644 AC: 982 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 276 AN: 3468

East Asian (EAS) AF: 0.0969 AC: 502 AN: 5178

South Asian (SAS) AF: 0.123 AC: 591 AN: 4820

European-Finnish (FIN) AF: 0.0529 AC: 560 AN: 10586

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

European-Non Finnish (NFE) AF: 0.108 AC: 7375 AN: 67992

Other (OTH) AF: 0.0796 AC: 168 AN: 2110

Alfa AF: 0.0408 Hom.: 24

Bravo AF: 0.0712

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.6
DANN	Benign	0.60
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs11854486; hg19: chr15-50952670;