rs11144134

Positions:

• chr9-74884880-T-C

Variant summary

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

The NM_017662.5(TRPM6):​c.33+2944A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 152,200 control chromosomes in the GnomAD database, including 355 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 0.060 (355 hom., cov: 33)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.32

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.33+2944A>G		intron_variant		ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.18+2751A>G		intron_variant			NP_001170781.1
TRPM6	NM_001177311.2	c.18+2351A>G		intron_variant			NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.33+2944A>G		intron_variant		1	NM_017662.5	ENSP00000354006.1
TRPM6	ENST00000361255.7	c.18+2351A>G		intron_variant		1		ENSP00000354962.3
TRPM6	ENST00000449912.6	c.18+2751A>G		intron_variant		1		ENSP00000396672.2
TRPM6	ENST00000359047.2	c.33+2944A>G		intron_variant		5		ENSP00000351942.2

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9127 AN: 152082 Hom.: 356 Cov.: 33

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0398

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.0753

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

GnomAD4 genome AF: 0.0600 AC: 9126 AN: 152200 Hom.: 355 Cov.: 33 AF XY: 0.0590 AC XY: 4393 AN XY: 74420

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.0806

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.0565

Gnomad4 NFE AF: 0.0860

Gnomad4 OTH AF: 0.0745

Alfa AF: 0.0772 Hom.: 253

Bravo AF: 0.0589

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.33
DANN	Benign	0.41

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: rs11144134; hg19: chr9-77499796;