9-74723807-AAT-A

Position:

• chr9-74723807-AAT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017662.5(TRPM6):​c.*804_*805del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.89 (55846 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: TRPM6 NM_017662.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.320

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 -10 ACMG points.

• BP6: Variant 9-74723807-AAT-A is Benign according to our data. Variant chr9-74723807-AAT-A is described in ClinVar as [Benign]. Clinvar id is 367279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM6	NM_017662.5	c.*804_*805del		3_prime_UTR_variant	39/39	ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2	c.*804_*805del		3_prime_UTR_variant	39/39		NP_001170781.1
TRPM6	NM_001177311.2	c.*804_*805del		3_prime_UTR_variant	39/39		NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6	c.*804_*805del		3_prime_UTR_variant	39/39	1	NM_017662.5	ENSP00000354006	P4
TRPM6	ENST00000361255.7	c.*804_*805del		3_prime_UTR_variant	39/39	1		ENSP00000354962	A2
TRPM6	ENST00000449912.6	c.*804_*805del		3_prime_UTR_variant	39/39	1		ENSP00000396672	A2

Frequencies

GnomAD3 genomes AF: 0.888 AC: 125358 AN: 141106 Hom.: 55855 Cov.: 0

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.891

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.885

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

GnomAD4 genome AF: 0.888 AC: 125343 AN: 141092 Hom.: 55846 Cov.: 0 AF XY: 0.883 AC XY: 60069 AN XY: 68000

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.846

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.884

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intestinal hypomagnesemia 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs143924458; hg19: chr9-77338723;