9-74723807-AAT-A

Variant names:

• chr9-74723807-AAT-A
• rs143924458
• NM_017662.5:c.*804_*805delAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017662.5(TRPM6):​c.*804_*805delAT 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
• Publications: 0 publications found

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]

TRPM6 Gene-Disease associations (from GenCC):

• intestinal hypomagnesemia 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017662.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM6	NM_017662.5	MANE Select	c.*804_*805delAT		3_prime_UTR	Exon 39 of 39	NP_060132.3
	TRPM6	NM_001177310.2		c.*804_*805delAT		3_prime_UTR	Exon 39 of 39	NP_001170781.1	Q9BX84-2
	TRPM6	NM_001177311.2		c.*804_*805delAT		3_prime_UTR	Exon 39 of 39	NP_001170782.1	Q9BX84-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM6	ENST00000360774.6	TSL:1 MANE Select	c.*804_*805delAT		3_prime_UTR	Exon 39 of 39	ENSP00000354006.1	Q9BX84-1
	TRPM6	ENST00000361255.7	TSL:1	c.*804_*805delAT		3_prime_UTR	Exon 39 of 39	ENSP00000354962.3	Q9BX84-3
	TRPM6	ENST00000449912.6	TSL:1	c.*804_*805delAT		3_prime_UTR	Exon 39 of 39	ENSP00000396672.2	Q9BX84-2

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

African (AFR) AF: 0.946 AC: 36374 AN: 38448

American (AMR) AF: 0.922 AC: 12670 AN: 13736

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3096 AN: 3406

East Asian (EAS) AF: 0.745 AC: 3671 AN: 4926

South Asian (SAS) AF: 0.846 AC: 3828 AN: 4524

European-Finnish (FIN) AF: 0.790 AC: 5731 AN: 7252

Middle Eastern (MID) AF: 0.892 AC: 248 AN: 278

European-Non Finnish (NFE) AF: 0.872 AC: 57314 AN: 65722

Other (OTH) AF: 0.884 AC: 1694 AN: 1916

Alfa AF: 0.832 Hom.: 1617

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Intestinal hypomagnesemia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs143924458; hg19: chr9-77338723; COSMIC: COSV104415996;