rs7173321

Variant names:

• chr15-50630403-C-G
• rs7173321
• NM_017672.6:c.1204+1014G>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.1204+1014G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,136 control chromosomes in the GnomAD database, including 1,350 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 0.12 (1350 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• 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)

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 (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.1204+1014G>C		intron_variant	Intron 10 of 38	ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.1204+1014G>C		intron_variant	Intron 10 of 38		NM_017672.6	ENSP00000495860.1
TRPM7	ENST00000560955.5	c.1204+1014G>C		intron_variant	Intron 10 of 38	1		ENSP00000453277.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18909 AN: 152018 Hom.: 1342 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0792

Gnomad EAS AF: 0.0985

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.125 AC: 18950 AN: 152136 Hom.: 1350 Cov.: 32 AF XY: 0.120 AC XY: 8958 AN XY: 74374

African (AFR) AF: 0.194 AC: 8058 AN: 41498

American (AMR) AF: 0.0815 AC: 1245 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0792 AC: 275 AN: 3472

East Asian (EAS) AF: 0.0982 AC: 507 AN: 5164

South Asian (SAS) AF: 0.122 AC: 587 AN: 4830

European-Finnish (FIN) AF: 0.0531 AC: 562 AN: 10586

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

European-Non Finnish (NFE) AF: 0.109 AC: 7379 AN: 67988

Other (OTH) AF: 0.112 AC: 238 AN: 2116

Alfa AF: 0.113 Hom.: 134

Bravo AF: 0.127

Asia WGS AF: 0.156 AC: 541 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	0.95
DANN	Benign	0.58
PhyloP100		-0.30
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: rs7173321; hg19: chr15-50922600;