rs539079

Variant names:

• chr9-74735668-T-C
• rs539079
• NM_017662.5:c.5776+2739A>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.5776+2739A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,262 control chromosomes in the GnomAD database, including 1,388 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 0.12 (1388 hom., cov: 32)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.5776+2739A>G		intron_variant	Intron 36 of 38	ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.5761+2739A>G		intron_variant	Intron 36 of 38		NP_001170781.1
TRPM6	NM_001177311.2	c.5761+2739A>G		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+2739A>G		intron_variant	Intron 36 of 38	1	NM_017662.5	ENSP00000354006.1
TRPM6	ENST00000361255.7	c.5761+2739A>G		intron_variant	Intron 36 of 38	1		ENSP00000354962.3
TRPM6	ENST00000449912.6	c.5761+2739A>G		intron_variant	Intron 36 of 38	1		ENSP00000396672.2
TRPM6	ENST00000715553.1	n.*40+1687A>G		intron_variant	Intron 37 of 39			ENSP00000520473.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18674 AN: 152144 Hom.: 1384 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.0616

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.123 AC: 18708 AN: 152262 Hom.: 1388 Cov.: 32 AF XY: 0.123 AC XY: 9164 AN XY: 74440

African (AFR) AF: 0.194 AC: 8071 AN: 41538

American (AMR) AF: 0.0895 AC: 1368 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 325 AN: 3472

East Asian (EAS) AF: 0.159 AC: 821 AN: 5176

South Asian (SAS) AF: 0.222 AC: 1069 AN: 4820

European-Finnish (FIN) AF: 0.0616 AC: 654 AN: 10612

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0888 AC: 6044 AN: 68032

Other (OTH) AF: 0.120 AC: 253 AN: 2114

Alfa AF: 0.111 Hom.: 173

Bravo AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.66
PhyloP100		0.21
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: rs539079; hg19: chr9-77350584;