rs4745363

Positions:

• chr9-74883239-T-A
• chr9-74883239-T-C
• chr9-74883239-T-G

Variant summary

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

The NM_017662.5(TRPM6):​c.33+4585A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,106 control chromosomes in the GnomAD database, including 12,013 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 0.37 (12013 hom., cov: 32)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.33+4585A>T		intron_variant		ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.18+4392A>T		intron_variant			NP_001170781.1
TRPM6	NM_001177311.2	c.18+3992A>T		intron_variant			NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.33+4585A>T		intron_variant		1	NM_017662.5	ENSP00000354006	P4
TRPM6	ENST00000361255.7	c.18+3992A>T		intron_variant		1		ENSP00000354962	A2
TRPM6	ENST00000449912.6	c.18+4392A>T		intron_variant		1		ENSP00000396672	A2
TRPM6	ENST00000359047.2	c.33+4585A>T		intron_variant		5		ENSP00000351942

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56270 AN: 151988 Hom.: 12009 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.370 AC: 56290 AN: 152106 Hom.: 12013 Cov.: 32 AF XY: 0.377 AC XY: 27992 AN XY: 74340

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.376

Alfa AF: 0.402 Hom.: 1659

Bravo AF: 0.356

Asia WGS AF: 0.462 AC: 1607 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.72

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: rs4745363; hg19: chr9-77498155;