9-74852321-A-G

Position:

• chr9-74852321-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.152+3206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 150,978 control chromosomes in the GnomAD database, including 8,504 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 0.31 (8504 hom., cov: 29)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.152+3206T>C		intron_variant		ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.137+3206T>C		intron_variant			NP_001170781.1
TRPM6	NM_001177311.2	c.137+3206T>C		intron_variant			NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.152+3206T>C		intron_variant		1	NM_017662.5	ENSP00000354006	P4
TRPM6	ENST00000361255.7	c.137+3206T>C		intron_variant		1		ENSP00000354962	A2
TRPM6	ENST00000449912.6	c.137+3206T>C		intron_variant		1		ENSP00000396672	A2
TRPM6	ENST00000359047.2	c.152+3206T>C		intron_variant		5		ENSP00000351942

Frequencies

GnomAD3 genomes AF: 0.311 AC: 46846 AN: 150870 Hom.: 8504 Cov.: 29

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.310 AC: 46865 AN: 150978 Hom.: 8504 Cov.: 29 AF XY: 0.317 AC XY: 23392 AN XY: 73696

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.313

Alfa AF: 0.229 Hom.: 615

Bravo AF: 0.297

Asia WGS AF: 0.447 AC: 1554 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.63

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: rs10869447; hg19: chr9-77467237;