Variant 12-113267845-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_017901.6(TPCN1):c.417C>T(p.Val139Val) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000692 in 1,612,694 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 4 hom. )

Consequence

TPCN1
NM_017901.6 splice_region, synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.130

Variant links:

Genes affected

TPCN1 (HGNC:18182): (two pore segment channel 1) Voltage-gated Ca(2+) and Na+ channels have 4 homologous domains, each containing 6 transmembrane segments, S1 to S6. TPCN1 is similar to these channels, but it has only 2 domains containing S1 to S6 (Ishibashi et al., 2000 [PubMed 10753632]).[supplied by OMIM, Mar 2008]

TPCN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 12-113267845-C-T is Benign according to our data. Variant chr12-113267845-C-T is described in ClinVar as [Benign]. Clinvar id is 773685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.13 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPCN1	NM_017901.6 link	c.417C>T	p.Val139Val	splice_region_variant, synonymous_variant	5/28	ENST00000335509.11	NP_060371.2	Q9ULQ1-1B3KSG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPCN1	ENST00000335509.11 link	c.417C>T	p.Val139Val	splice_region_variant, synonymous_variant	5/28	1	NM_017901.6	ENSP00000335300.6		Q9ULQ1-1

Frequencies

GnomAD3 genomes

AF:

0.00376

AC:

572

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000976

AC:

245

AN:

251038

Hom.:

AF XY:

0.000656

AC XY:

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.000371

AC:

542

AN:

1460476

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

235

AN XY:

726632

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.00377

AC:

574

AN:

152218

Hom.:

Cov.:

AF XY:

0.00359

AC XY:

267

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00224

Hom.:

Bravo

AF:

0.00462

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

3.6

DANN

Benign

0.58

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