9-74743052-C-T

Position:

• chr9-74743052-C-T

Variant summary

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

The ENST00000360774.6(TRPM6):​c.5135-426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,108 control chromosomes in the GnomAD database, including 7,214 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 0.23 (7214 hom., cov: 33)
• Consequence: TRPM6 ENST00000360774.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.5135-426G>A		intron_variant		ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.5120-426G>A		intron_variant			NP_001170781.1
TRPM6	NM_001177311.2	c.5120-426G>A		intron_variant			NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.5135-426G>A		intron_variant		1	NM_017662.5	ENSP00000354006	P4
TRPM6	ENST00000361255.7	c.5120-426G>A		intron_variant		1		ENSP00000354962	A2
TRPM6	ENST00000449912.6	c.5120-426G>A		intron_variant		1		ENSP00000396672	A2

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34763 AN: 151990 Hom.: 7181 Cov.: 33

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.0616

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0903

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.229 AC: 34868 AN: 152108 Hom.: 7214 Cov.: 33 AF XY: 0.225 AC XY: 16713 AN XY: 74364

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.0616

Gnomad4 NFE AF: 0.0903

Gnomad4 OTH AF: 0.193

Alfa AF: 0.103 Hom.: 2530

Bravo AF: 0.248

Asia WGS AF: 0.219 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs877809; hg19: chr9-77357968;