rs1123608

Variant names:

• chr11-69135852-G-T
• rs1123608
• ENST00000637084.1:n.*511+320G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 0 publications found

Genes affected

ENSG00000287725 (HGNC:):

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000287725	ENST00000637084.1	TSL:1	n.*511+320G>T		intron	N/A	ENSP00000490615.1	A0A1B0GVQ7
	TPCN2	ENST00000637342.1	TSL:5	c.*324G>T		3_prime_UTR	Exon 23 of 23	ENSP00000490171.1	A0A1B0GUM5
	TPCN2	ENST00000637504.1	TSL:5	c.*451G>T		3_prime_UTR	Exon 20 of 20	ENSP00000489759.1	A0A1B0GTM1

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7495 AN: 152162 Hom.: 305 Cov.: 33

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.: 0 AF XY: 0.0506 AC XY: 1368 AN XY: 27032

African (AFR) AF: 0.0437 AC: 94 AN: 2152

American (AMR) AF: 0.116 AC: 171 AN: 1472

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 82 AN: 2456

East Asian (EAS) AF: 0.240 AC: 1048 AN: 4364

South Asian (SAS) AF: 0.120 AC: 60 AN: 502

European-Finnish (FIN) AF: 0.0507 AC: 144 AN: 2840

Middle Eastern (MID) AF: 0.0304 AC: 11 AN: 362

European-Non Finnish (NFE) AF: 0.0298 AC: 1066 AN: 35828

Other (OTH) AF: 0.0476 AC: 188 AN: 3952

GnomAD4 genome AF: 0.0492 AC: 7493 AN: 152280 Hom.: 303 Cov.: 33 AF XY: 0.0525 AC XY: 3907 AN XY: 74462

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: 75 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: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0295 AC: 2009 AN: 68020

Other (OTH) AF: 0.0455 AC: 96 AN: 2112

Alfa AF: 0.0364 Hom.: 49

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
DANN	Benign	0.82
PhyloP100		-0.34

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1123608;

hg19: chr11-68903320;