rs10512038

Variant names:

• chr9-74805310-T-C
• rs10512038
• NM_017662.5:c.1639-1424A>G

Variant summary

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

The NM_017662.5(TRPM6):​c.1639-1424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,032 control chromosomes in the GnomAD database, including 6,009 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 0.27 (6009 hom., cov: 32)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 4 publications found

Genes affected

TRPM6 (HGNC:17995): (transient receptor potential cation channel subfamily M member 6) This gene is predominantly expressed in the kidney and colon, and encodes a protein containing an ion channel domain and a protein kinase domain. It is crucial for magnesium homeostasis, and plays an essential role in epithelial magnesium transport and in the active magnesium absorption in the gut and kidney. Mutations in this gene are associated with hypomagnesemia with secondary hypocalcemia. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Apr 2010]

TRPM6 Gene-Disease associations (from GenCC):

• intestinal hypomagnesemia 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.1639-1424A>G		intron_variant	Intron 14 of 38	ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.1624-1424A>G		intron_variant	Intron 14 of 38		NP_001170781.1
TRPM6	NM_001177311.2	c.1624-1424A>G		intron_variant	Intron 14 of 38		NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.1639-1424A>G		intron_variant	Intron 14 of 38	1	NM_017662.5	ENSP00000354006.1
TRPM6	ENST00000361255.7	c.1624-1424A>G		intron_variant	Intron 14 of 38	1		ENSP00000354962.3
TRPM6	ENST00000449912.6	c.1624-1424A>G		intron_variant	Intron 14 of 38	1		ENSP00000396672.2
TRPM6	ENST00000715553.1	n.1639-1424A>G		intron_variant	Intron 14 of 39			ENSP00000520473.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41251 AN: 151912 Hom.: 5999 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.272 AC: 41305 AN: 152032 Hom.: 6009 Cov.: 32 AF XY: 0.267 AC XY: 19846 AN XY: 74306

African (AFR) AF: 0.376 AC: 15582 AN: 41454

American (AMR) AF: 0.206 AC: 3138 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3468

East Asian (EAS) AF: 0.142 AC: 733 AN: 5170

South Asian (SAS) AF: 0.256 AC: 1235 AN: 4816

European-Finnish (FIN) AF: 0.227 AC: 2397 AN: 10576

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16555 AN: 67972

Other (OTH) AF: 0.249 AC: 525 AN: 2108

Alfa AF: 0.236 Hom.: 1194

Bravo AF: 0.276

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.55
PhyloP100		-1.3
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: rs10512038; hg19: chr9-77420226;