X-15673898-T-A

Variant names:

• chrX-15673898-T-A
• rs5934262
• ENST00000649243.1:n.-99+1545A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000649243.1(ENSG00000285602):​n.-99+1545A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.59 (13932 hom., 19684 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000285602 ENST00000649243.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 1 publications found

Genes affected

ENSG00000285602 (HGNC:):

CLTRN (HGNC:29437): (collectrin, amino acid transport regulator) This gene encodes a type 1 transmembrane protein that is important for trafficking amino acid transporters to the apical brush border of proximal tubules. The encoded protein binds to amino acid transporters and regulates their expression on the plasma membrane. It also plays a role in controlling insulin exocytosis by regulating formation of the SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor) complex in pancreatic beta cells. The extracellular domain of the encoded protein may be cleaved and shed from the plasma membrane specifically in pancreatic beta cells. [provided by RefSeq, Jun 2013]

CLTRN Gene-Disease associations (from GenCC):

• Hartnup disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLTRN	XM_017029680.2	c.-99+1545A>T		intron_variant	Intron 1 of 5		XP_016885169.1
CLTRN	XM_024452411.2	c.-99+1091A>T		intron_variant	Intron 1 of 5		XP_024308179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285602	ENST00000649243.1	n.-99+1545A>T		intron_variant	Intron 1 of 19			ENSP00000497489.1
CLTRN	ENST00000650271.1	c.-506+1091A>T		intron_variant	Intron 1 of 6			ENSP00000497814.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 64940 AN: 110991 Hom.: 13914 Cov.: 24

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.470

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.584

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.586 AC: 65020 AN: 111044 Hom.: 13932 Cov.: 24 AF XY: 0.591 AC XY: 19684 AN XY: 33292

African (AFR) AF: 0.711 AC: 21689 AN: 30513

American (AMR) AF: 0.679 AC: 7140 AN: 10518

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1308 AN: 2634

East Asian (EAS) AF: 0.939 AC: 3334 AN: 3550

South Asian (SAS) AF: 0.670 AC: 1816 AN: 2709

European-Finnish (FIN) AF: 0.513 AC: 3012 AN: 5873

Middle Eastern (MID) AF: 0.491 AC: 105 AN: 214

European-Non Finnish (NFE) AF: 0.480 AC: 25359 AN: 52853

Other (OTH) AF: 0.590 AC: 891 AN: 1510

Alfa AF: 0.312 Hom.: 1307

Bravo AF: 0.610

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.088

Splicing

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

Other links and lift over

dbSNP: rs5934262; hg19: chrX-15692021;