rs4745363

Variant names:

• chr9-74883239-T-A
• rs4745363
• NM_017662.5:c.33+4585A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-74883239-T-A
• chr9-74883239-T-C
• chr9-74883239-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017662.5(TRPM6):​c.33+4585A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,106 control chromosomes in the GnomAD database, including 12,013 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 0.37 (12013 hom., cov: 32)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 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.33+4585A>T		intron	N/A	NP_060132.3
	TRPM6	NM_001177310.2		c.18+4392A>T		intron	N/A	NP_001170781.1	Q9BX84-2
	TRPM6	NM_001177311.2		c.18+3992A>T		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.33+4585A>T		intron	N/A	ENSP00000354006.1	Q9BX84-1
	TRPM6	ENST00000361255.7	TSL:1	c.18+3992A>T		intron	N/A	ENSP00000354962.3	Q9BX84-3
	TRPM6	ENST00000449912.6	TSL:1	c.18+4392A>T		intron	N/A	ENSP00000396672.2	Q9BX84-2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56270 AN: 151988 Hom.: 12009 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.370 AC: 56290 AN: 152106 Hom.: 12013 Cov.: 32 AF XY: 0.377 AC XY: 27992 AN XY: 74340

African (AFR) AF: 0.151 AC: 6281 AN: 41510

American (AMR) AF: 0.463 AC: 7079 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1278 AN: 3468

East Asian (EAS) AF: 0.498 AC: 2573 AN: 5170

South Asian (SAS) AF: 0.485 AC: 2341 AN: 4830

European-Finnish (FIN) AF: 0.468 AC: 4950 AN: 10572

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30376 AN: 67956

Other (OTH) AF: 0.376 AC: 791 AN: 2106

Alfa AF: 0.402 Hom.: 1659

Bravo AF: 0.356

Asia WGS AF: 0.462 AC: 1607 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		-0.62
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: rs4745363; hg19: chr9-77498155;