rs1327824

Positions:

• chr9-74745006-C-G

Variant summary

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

The NM_017662.5(TRPM6):​c.5084-861G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 152,292 control chromosomes in the GnomAD database, including 430 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 0.072 (430 hom., cov: 32)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.5084-861G>C		intron_variant		ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.5069-861G>C		intron_variant			NP_001170781.1
TRPM6	NM_001177311.2	c.5069-861G>C		intron_variant			NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.5084-861G>C		intron_variant		1	NM_017662.5	ENSP00000354006	P4
TRPM6	ENST00000361255.7	c.5069-861G>C		intron_variant		1		ENSP00000354962	A2
TRPM6	ENST00000449912.6	c.5069-861G>C		intron_variant		1		ENSP00000396672	A2

Frequencies

GnomAD3 genomes AF: 0.0718 AC: 10931 AN: 152174 Hom.: 432 Cov.: 32

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.0652

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.0568

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

GnomAD4 genome AF: 0.0718 AC: 10935 AN: 152292 Hom.: 430 Cov.: 32 AF XY: 0.0704 AC XY: 5242 AN XY: 74462

Gnomad4 AFR AF: 0.0435

Gnomad4 AMR AF: 0.0838

Gnomad4 ASJ AF: 0.0652

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0755

Gnomad4 FIN AF: 0.0532

Gnomad4 NFE AF: 0.0843

Gnomad4 OTH AF: 0.0586

Alfa AF: 0.0739 Hom.: 43

Bravo AF: 0.0741

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.69
DANN	Benign	0.32

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: rs1327824; hg19: chr9-77359922;