9-74800368-A-T

Variant names:

• chr9-74800368-A-T
• rs7859201
• NM_017662.5:c.2124T>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_017662.5(TRPM6):​c.2124T>A​(p.Leu708Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L708L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TRPM6 NM_017662.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390

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]

RN7SKP47 (HGNC:45771): (RN7SK pseudogene 47)

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.39 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.2124T>A	p.Leu708Leu	synonymous_variant	Exon 17 of 39	ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.2109T>A	p.Leu703Leu	synonymous_variant	Exon 17 of 39		NP_001170781.1
TRPM6	NM_001177311.2	c.2109T>A	p.Leu703Leu	synonymous_variant	Exon 17 of 39		NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.2124T>A	p.Leu708Leu	synonymous_variant	Exon 17 of 39	1	NM_017662.5	ENSP00000354006.1
TRPM6	ENST00000361255.7	c.2109T>A	p.Leu703Leu	synonymous_variant	Exon 17 of 39	1		ENSP00000354962.3
TRPM6	ENST00000449912.6	c.2109T>A	p.Leu703Leu	synonymous_variant	Exon 17 of 39	1		ENSP00000396672.2
RN7SKP47	ENST00000365347.1	n.*146A>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.7
DANN	Benign	0.67

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: rs7859201; hg19: chr9-77415284;