Genetic Variant ENSG00000287725:n.*511+320G>T (chr11-69135852-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000637084.1(ENSG00000287725):n.*511+320G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 206,208 control chromosomes in the GnomAD database, including 472 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.049 ( 303 hom., cov: 33)

Exomes 𝑓: 0.053 ( 169 hom. )

Consequence

ENSG00000287725
ENST00000637084.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.341

Publications

0 publications found

Variant links:

Genes affected

ENSG00000287725 (HGNC:):

ENSG00000287725 links:

TPCN2 (HGNC:20820): (two pore segment channel 2) This gene encodes a putative cation-selective ion channel with two repeats of a six-transmembrane-domain. The protein localizes to lysosomal membranes and enables nicotinic acid adenine dinucleotide phosphate (NAADP) -induced calcium ion release from lysosome-related stores. This ubiquitously expressed gene has elevated expression in liver and kidney. Two common nonsynonymous SNPs in this gene strongly associate with blond versus brown hair pigmentation.[provided by RefSeq, Dec 2009]

TPCN2 Gene-Disease associations (from GenCC):

albinism
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

TPCN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000637084.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ENSG00000287725	ENST00000637084.1	TSL:1	n.*511+320G>T	intron	N/A	ENSP00000490615.1
TPCN2	ENST00000637342.1	TSL:5	c.*324G>T	3_prime_UTR	Exon 23 of 23	ENSP00000490171.1
TPCN2	ENST00000637504.1	TSL:5	c.*451G>T	3_prime_UTR	Exon 20 of 20	ENSP00000489759.1

Frequencies

GnomAD3 genomes

AF:

0.0493

AC:

7495

AN:

152162

Hom.:

305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0466

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0954

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0377

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0295

Gnomad OTH

AF:

0.0450

GnomAD4 exome

AF:

0.0531

AC:

2864

AN:

53928

Hom.:

169

Cov.:

AF XY:

0.0506

AC XY:

1368

AN XY:

27032

show subpopulations

African (AFR)

AF:

0.0437

AC:

AN:

2152

American (AMR)

AF:

0.116

AC:

171

AN:

1472

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

AN:

2456

East Asian (EAS)

AF:

0.240

AC:

1048

AN:

4364

South Asian (SAS)

AF:

0.120

AC:

AN:

502

European-Finnish (FIN)

AF:

0.0507

AC:

144

AN:

2840

Middle Eastern (MID)

AF:

0.0304

AC:

AN:

362

European-Non Finnish (NFE)

AF:

0.0298

AC:

1066

AN:

35828

Other (OTH)

AF:

0.0476

AC:

188

AN:

3952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

127

254

381

508

635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0492

AC:

7493

AN:

152280

Hom.:

303

Cov.:

AF XY:

0.0525

AC XY:

3907

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0464

AC:

1931

AN:

41572

American (AMR)

AF:

0.0953

AC:

1458

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3472

East Asian (EAS)

AF:

0.192

AC:

990

AN:

5164

South Asian (SAS)

AF:

0.107

AC:

517

AN:

4822

European-Finnish (FIN)

AF:

0.0377

AC:

400

AN:

10612

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0295

AC:

2009

AN:

68020

Other (OTH)

AF:

0.0455

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

350

701

1051

1402

1752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0364

Hom.:

Bravo

AF:

0.0527

Asia WGS

AF:

0.141

AC:

492

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.7

(source)

DANN

Benign

0.82

PhyloP100

-0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over