9-74800084-T-C

Variant names:

• chr9-74800084-T-C
• rs12336062
• NM_017662.5:c.2238+170A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017662.5(TRPM6):​c.2238+170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 658,114 control chromosomes in the GnomAD database, including 57,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17365 hom., cov: 31)
  • Exomes 𝑓: 0.39 (39988 hom.)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.23
• Publications: 1 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]

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 9-74800084-T-C is Benign according to our data. Variant chr9-74800084-T-C is described in ClinVar as Benign. ClinVar VariationId is 1269145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 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.2238+170A>G		intron	N/A	NP_060132.3
	TRPM6	NM_001177310.2		c.2223+170A>G		intron	N/A	NP_001170781.1	Q9BX84-2
	TRPM6	NM_001177311.2		c.2223+170A>G		intron	N/A	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.2238+170A>G		intron	N/A	ENSP00000354006.1	Q9BX84-1
	TRPM6	ENST00000361255.7	TSL:1	c.2223+170A>G		intron	N/A	ENSP00000354962.3	Q9BX84-3
	TRPM6	ENST00000449912.6	TSL:1	c.2223+170A>G		intron	N/A	ENSP00000396672.2	Q9BX84-2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69472 AN: 151832 Hom.: 17338 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.392 AC: 198186 AN: 506164 Hom.: 39988 Cov.: 6 AF XY: 0.392 AC XY: 105718 AN XY: 269394

African (AFR) AF: 0.671 AC: 9299 AN: 13856

American (AMR) AF: 0.304 AC: 7903 AN: 26016

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 5667 AN: 15480

East Asian (EAS) AF: 0.352 AC: 11011 AN: 31292

South Asian (SAS) AF: 0.424 AC: 21094 AN: 49796

European-Finnish (FIN) AF: 0.411 AC: 14060 AN: 34242

Middle Eastern (MID) AF: 0.359 AC: 757 AN: 2106

European-Non Finnish (NFE) AF: 0.384 AC: 117142 AN: 305380

Other (OTH) AF: 0.402 AC: 11253 AN: 27996

GnomAD4 genome AF: 0.458 AC: 69561 AN: 151950 Hom.: 17365 Cov.: 31 AF XY: 0.455 AC XY: 33787 AN XY: 74256

African (AFR) AF: 0.668 AC: 27655 AN: 41408

American (AMR) AF: 0.353 AC: 5384 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1757 AN: 5150

South Asian (SAS) AF: 0.412 AC: 1981 AN: 4806

European-Finnish (FIN) AF: 0.412 AC: 4356 AN: 10560

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25878 AN: 67972

Other (OTH) AF: 0.403 AC: 850 AN: 2108

Alfa AF: 0.420 Hom.: 2251

Bravo AF: 0.462

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.30
PhyloP100		-1.2
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: rs12336062; hg19: chr9-77415000;