rs875034

chr9-74742127-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017662.5(TRPM6):c.5200+434T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,014 control chromosomes in the GnomAD database, including 23,636 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 0.53 (23636 hom., cov: 32)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• 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/exons	MANE	UniProt
TRPM6	NM_017662.5	c.5200+434T>C		intron_variant		ENST00000360774.6
TRPM6	NM_001177310.2	c.5185+434T>C		intron_variant
TRPM6	NM_001177311.2	c.5185+434T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM6	ENST00000360774.6	c.5200+434T>C		intron_variant		1	NM_017662.5	P4
TRPM6	ENST00000361255.7	c.5185+434T>C		intron_variant		1		A2
TRPM6	ENST00000449912.6	c.5185+434T>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79961 AN: 151896 Hom.: 23593 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.527 AC: 80061 AN: 152014 Hom.: 23636 Cov.: 32 AF XY: 0.517 AC XY: 38422 AN XY: 74294

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.540

Alfa AF: 0.482 Hom.: 4150

Bravo AF: 0.539

Asia WGS AF: 0.315 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	13
Dann	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs875034; hg19: chr9-77357043;