rs539079

Positions:

• chr9-74735668-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000360774.6(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 ENST00000360774.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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 -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/exons	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.5776+2739A>G		intron_variant		ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.5761+2739A>G		intron_variant			NP_001170781.1
TRPM6	NM_001177311.2	c.5761+2739A>G		intron_variant			NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.5776+2739A>G		intron_variant		1	NM_017662.5	ENSP00000354006	P4
TRPM6	ENST00000361255.7	c.5761+2739A>G		intron_variant		1		ENSP00000354962	A2
TRPM6	ENST00000449912.6	c.5761+2739A>G		intron_variant		1		ENSP00000396672	A2

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

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0895

Gnomad4 ASJ AF: 0.0936

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.0616

Gnomad4 NFE AF: 0.0888

Gnomad4 OTH AF: 0.120

Alfa AF: 0.108 Hom.: 164

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

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: rs539079; hg19: chr9-77350584;