rs11854949

Variant names:

• chr15-50686144-T-G
• rs11854949
• NM_017672.6:c.3+387A>C

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+387A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 152,246 control chromosomes in the GnomAD database, including 573 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 0.078 (573 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 3 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=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.3+387A>C		intron_variant	Intron 1 of 38	ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.3+387A>C		intron_variant	Intron 1 of 38		NM_017672.6	ENSP00000495860.1
TRPM7	ENST00000560955.5	c.3+387A>C		intron_variant	Intron 1 of 38	1		ENSP00000453277.1
ENSG00000288645	ENST00000676296.1	c.187+387A>C		intron_variant	Intron 1 of 3			ENSP00000502268.1

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11857 AN: 152128 Hom.: 571 Cov.: 32

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.0968

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0962

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0784

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

GnomAD4 genome AF: 0.0780 AC: 11871 AN: 152246 Hom.: 573 Cov.: 32 AF XY: 0.0762 AC XY: 5674 AN XY: 74436

African (AFR) AF: 0.0306 AC: 1273 AN: 41548

American (AMR) AF: 0.0653 AC: 998 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3470

East Asian (EAS) AF: 0.0964 AC: 498 AN: 5164

South Asian (SAS) AF: 0.123 AC: 592 AN: 4822

European-Finnish (FIN) AF: 0.0531 AC: 563 AN: 10610

Middle Eastern (MID) AF: 0.0966 AC: 28 AN: 290

European-Non Finnish (NFE) AF: 0.109 AC: 7397 AN: 68024

Other (OTH) AF: 0.0833 AC: 176 AN: 2114

Alfa AF: 0.0868 Hom.: 69

Bravo AF: 0.0740

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.069
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: rs11854949; hg19: chr15-50978341;