rs3858116

Variant names:

• chr9-74796023-G-A
• rs3858116
• NM_017662.5:c.2391+718C>T

Variant summary

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

The NM_017662.5(TRPM6):​c.2391+718C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,960 control chromosomes in the GnomAD database, including 20,478 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 0.48 (20478 hom., cov: 32)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.2391+718C>T		intron_variant	Intron 18 of 38	ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.2376+718C>T		intron_variant	Intron 18 of 38		NP_001170781.1
TRPM6	NM_001177311.2	c.2376+718C>T		intron_variant	Intron 18 of 38		NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.2391+718C>T		intron_variant	Intron 18 of 38	1	NM_017662.5	ENSP00000354006.1
TRPM6	ENST00000361255.7	c.2376+718C>T		intron_variant	Intron 18 of 38	1		ENSP00000354962.3
TRPM6	ENST00000449912.6	c.2376+718C>T		intron_variant	Intron 18 of 38	1		ENSP00000396672.2
TRPM6	ENST00000715553.1	n.2391+718C>T		intron_variant	Intron 18 of 39			ENSP00000520473.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72550 AN: 151842 Hom.: 20428 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.478 AC: 72666 AN: 151960 Hom.: 20478 Cov.: 32 AF XY: 0.474 AC XY: 35197 AN XY: 74254

African (AFR) AF: 0.797 AC: 33069 AN: 41472

American (AMR) AF: 0.338 AC: 5145 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1202 AN: 3470

East Asian (EAS) AF: 0.340 AC: 1756 AN: 5160

South Asian (SAS) AF: 0.413 AC: 1988 AN: 4816

European-Finnish (FIN) AF: 0.385 AC: 4049 AN: 10530

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24200 AN: 67956

Other (OTH) AF: 0.415 AC: 875 AN: 2110

Alfa AF: 0.404 Hom.: 2867

Bravo AF: 0.487

Asia WGS AF: 0.398 AC: 1388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.49
DANN	Benign	0.44
PhyloP100		-0.62
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: rs3858116; hg19: chr9-77410939;