9-74781739-C-T

Position:

• chr9-74781739-C-T

Variant summary

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

The NM_017662.5(TRPM6):​c.3209+623G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,772 control chromosomes in the GnomAD database, including 11,689 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 0.39 (11689 hom., cov: 30)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM6	NM_017662.5	c.3209+623G>A		intron_variant		ENST00000360774.6
TRPM6	NM_001177310.2	c.3194+623G>A		intron_variant
TRPM6	NM_001177311.2	c.3194+623G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM6	ENST00000360774.6	c.3209+623G>A		intron_variant		1	NM_017662.5	P4
TRPM6	ENST00000361255.7	c.3194+623G>A		intron_variant		1		A2
TRPM6	ENST00000449912.6	c.3194+623G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59142 AN: 151654 Hom.: 11690 Cov.: 30

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.390 AC: 59170 AN: 151772 Hom.: 11689 Cov.: 30 AF XY: 0.387 AC XY: 28702 AN XY: 74150

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.415

Alfa AF: 0.407 Hom.: 26735

Bravo AF: 0.386

Asia WGS AF: 0.361 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.77
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6560408; hg19: chr9-77396655;