rs944857

Variant names:

• chr9-74737882-A-G
• rs944857
• NM_017662.5:c.5776+525T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-74737882-A-G
• chr9-74737882-A-T

Variant summary

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

The NM_017662.5(TRPM6):​c.5776+525T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,108 control chromosomes in the GnomAD database, including 6,990 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 0.26 (6990 hom., cov: 32)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.5776+525T>C		intron_variant	Intron 36 of 38	ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.5761+525T>C		intron_variant	Intron 36 of 38		NP_001170781.1
TRPM6	NM_001177311.2	c.5761+525T>C		intron_variant	Intron 36 of 38		NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.5776+525T>C		intron_variant	Intron 36 of 38	1	NM_017662.5	ENSP00000354006.1
TRPM6	ENST00000361255.7	c.5761+525T>C		intron_variant	Intron 36 of 38	1		ENSP00000354962.3
TRPM6	ENST00000449912.6	c.5761+525T>C		intron_variant	Intron 36 of 38	1		ENSP00000396672.2
TRPM6	ENST00000715553.1	n.5777-432T>C		intron_variant	Intron 36 of 39			ENSP00000520473.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39028 AN: 151988 Hom.: 6960 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.257 AC: 39127 AN: 152108 Hom.: 6990 Cov.: 32 AF XY: 0.251 AC XY: 18658 AN XY: 74378

African (AFR) AF: 0.502 AC: 20832 AN: 41458

American (AMR) AF: 0.275 AC: 4206 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 654 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.0534 AC: 258 AN: 4830

European-Finnish (FIN) AF: 0.142 AC: 1506 AN: 10582

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10976 AN: 67986

Other (OTH) AF: 0.218 AC: 462 AN: 2116

Alfa AF: 0.174 Hom.: 3297

Bravo AF: 0.280

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.0
DANN	Benign	0.67
PhyloP100		0.11
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: rs944857; hg19: chr9-77352798;