Variant 9-74827700-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017662.5(TRPM6):c.841+78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,483,244 control chromosomes in the GnomAD database, including 255,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27311 hom., cov: 29)

Exomes 𝑓: 0.58 ( 228365 hom. )

Consequence

TRPM6
NM_017662.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.91

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 9-74827700-C-T is Benign according to our data. Variant chr9-74827700-C-T is described in ClinVar as [Benign]. Clinvar id is 1236618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-74827700-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
TRPM6	NM_017662.5 linkuse as main transcript	c.841+78G>A	intron_variant	ENST00000360774.6	NP_060132.3
TRPM6	NM_001177310.2 linkuse as main transcript	c.826+78G>A	intron_variant		NP_001170781.1
TRPM6	NM_001177311.2 linkuse as main transcript	c.826+78G>A	intron_variant		NP_001170782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM6	ENST00000360774.6 linkuse as main transcript	c.841+78G>A		intron_variant		1	NM_017662.5	ENSP00000354006	P4	Q9BX84-1

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90327

AN:

151362

Hom.:

27255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.648

Gnomad AMI

AF:

0.620

Gnomad AMR

AF:

0.582

Gnomad ASJ

AF:

0.485

Gnomad EAS

AF:

0.795

Gnomad SAS

AF:

0.706

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.563

Gnomad OTH

AF:

0.554

GnomAD3 exomes

AF:

0.614

AC:

152526

AN:

248538

Hom.:

47694

AF XY:

0.613

AC XY:

82375

AN XY:

134478

show subpopulations

Gnomad AFR exome

AF:

0.654

Gnomad AMR exome

AF:

0.659

Gnomad ASJ exome

AF:

0.481

Gnomad EAS exome

AF:

0.815

Gnomad SAS exome

AF:

0.707

Gnomad FIN exome

AF:

0.540

Gnomad NFE exome

AF:

0.563

Gnomad OTH exome

AF:

0.578

GnomAD4 exome

AF:

0.583

AC:

775842

AN:

1331764

Hom.:

228365

Cov.:

AF XY:

0.585

AC XY:

391806

AN XY:

669286

show subpopulations

Gnomad4 AFR exome

AF:

0.646

Gnomad4 AMR exome

AF:

0.652

Gnomad4 ASJ exome

AF:

0.488

Gnomad4 EAS exome

AF:

0.793

Gnomad4 SAS exome

AF:

0.706

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.564

Gnomad4 OTH exome

AF:

0.578

GnomAD4 genome

AF:

0.597

AC:

90450

AN:

151480

Hom.:

27311

Cov.:

AF XY:

0.598

AC XY:

44238

AN XY:

73976

show subpopulations

Gnomad4 AFR

AF:

0.649

Gnomad4 AMR

AF:

0.582

Gnomad4 ASJ

AF:

0.485

Gnomad4 EAS

AF:

0.795

Gnomad4 SAS

AF:

0.707

Gnomad4 FIN

AF:

0.539

Gnomad4 NFE

AF:

0.563

Gnomad4 OTH

AF:

0.560

Alfa

AF:

0.564

Hom.:

48549

Bravo

AF:

0.602

Asia WGS

AF:

0.723

AC:

2514

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.13

DANN

Benign

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over