rs514348

Variant names:

• chr9-74727947-A-T
• rs514348
• NM_017662.5:c.5935+292T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-74727947-A-T
• chr9-74727947-A-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

TRPM6 Gene-Disease associations (from GenCC):

• intestinal hypomagnesemia 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017662.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM6	NM_017662.5	MANE Select	c.5935+292T>A		intron	N/A	NP_060132.3
	TRPM6	NM_001177310.2		c.5920+292T>A		intron	N/A	NP_001170781.1	Q9BX84-2
	TRPM6	NM_001177311.2		c.5920+292T>A		intron	N/A	NP_001170782.1	Q9BX84-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM6	ENST00000360774.6	TSL:1 MANE Select	c.5935+292T>A		intron	N/A	ENSP00000354006.1	Q9BX84-1
	TRPM6	ENST00000361255.7	TSL:1	c.5920+292T>A		intron	N/A	ENSP00000354962.3	Q9BX84-3
	TRPM6	ENST00000449912.6	TSL:1	c.5920+292T>A		intron	N/A	ENSP00000396672.2	Q9BX84-2

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

African (AFR) AF: 0.862 AC: 35745 AN: 41484

American (AMR) AF: 0.542 AC: 8269 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2150 AN: 3466

East Asian (EAS) AF: 0.480 AC: 2462 AN: 5132

South Asian (SAS) AF: 0.608 AC: 2918 AN: 4802

European-Finnish (FIN) AF: 0.526 AC: 5549 AN: 10548

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40363 AN: 67946

Other (OTH) AF: 0.660 AC: 1394 AN: 2112

Alfa AF: 0.628 Hom.: 3840

Bravo AF: 0.666

Asia WGS AF: 0.551 AC: 1918 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.53
PhyloP100		-0.060
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs514348; hg19: chr9-77342863;