9-74727947-A-T

Position:

• chr9-74727947-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017662.5(TRPM6):​c.5935+292T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,962 control chromosomes in the GnomAD database, including 34,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (34111 hom., cov: 30)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0600

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-74727947-A-T is Benign according to our data. Variant chr9-74727947-A-T is described in ClinVar as [Benign]. Clinvar id is 1221845.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.5935+292T>A		intron_variant		ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.5920+292T>A		intron_variant			NP_001170781.1
TRPM6	NM_001177311.2	c.5920+292T>A		intron_variant			NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.5935+292T>A		intron_variant		1	NM_017662.5	ENSP00000354006.1
TRPM6	ENST00000361255.7	c.5920+292T>A		intron_variant		1		ENSP00000354962.3
TRPM6	ENST00000449912.6	c.5920+292T>A		intron_variant		1		ENSP00000396672.2

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99499 AN: 151844 Hom.: 34063 Cov.: 30

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.655 AC: 99600 AN: 151962 Hom.: 34111 Cov.: 30 AF XY: 0.646 AC XY: 47968 AN XY: 74254

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.660

Alfa AF: 0.628 Hom.: 3840

Bravo AF: 0.666

Asia WGS AF: 0.551 AC: 1918 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.53

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: rs514348; hg19: chr9-77342863;