rs2151423

Variant names:

• chr9-74791089-A-G
• rs2151423
• NM_017662.5:c.2538+1535T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-74791089-A-G
• chr9-74791089-A-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.2538+1535T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,092 control chromosomes in the GnomAD database, including 19,614 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 0.50 (19614 hom., cov: 32)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566
• 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 (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.2538+1535T>C		intron_variant	Intron 19 of 38	ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.2523+1535T>C		intron_variant	Intron 19 of 38		NP_001170781.1
TRPM6	NM_001177311.2	c.2523+1535T>C		intron_variant	Intron 19 of 38		NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.2538+1535T>C		intron_variant	Intron 19 of 38	1	NM_017662.5	ENSP00000354006.1
TRPM6	ENST00000361255.7	c.2523+1535T>C		intron_variant	Intron 19 of 38	1		ENSP00000354962.3
TRPM6	ENST00000449912.6	c.2523+1535T>C		intron_variant	Intron 19 of 38	1		ENSP00000396672.2
TRPM6	ENST00000715553.1	n.2538+1535T>C		intron_variant	Intron 19 of 39			ENSP00000520473.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76588 AN: 151974 Hom.: 19570 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.504 AC: 76698 AN: 152092 Hom.: 19614 Cov.: 32 AF XY: 0.506 AC XY: 37603 AN XY: 74334

African (AFR) AF: 0.572 AC: 23717 AN: 41484

American (AMR) AF: 0.555 AC: 8474 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1552 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3107 AN: 5170

South Asian (SAS) AF: 0.600 AC: 2899 AN: 4834

European-Finnish (FIN) AF: 0.459 AC: 4846 AN: 10560

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30635 AN: 67978

Other (OTH) AF: 0.471 AC: 994 AN: 2112

Alfa AF: 0.483 Hom.: 7473

Bravo AF: 0.511

Asia WGS AF: 0.614 AC: 2133 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	1.5
DANN	Benign	0.78
PhyloP100		-0.57
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: rs2151423; hg19: chr9-77406005;