rs1477455320

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020665.6(CLTRN):c.524A>G(p.Glu175Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,091,111 control chromosomes in the GnomAD database, including 1 homozygotes. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000026 ( 1 hom. 8 hem. )

Consequence

CLTRN
NM_020665.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20

Publications

0 publications found

Variant links:

Genes affected

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

CLTRN links:

ENSG00000285602 (HGNC:):

ENSG00000285602 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059186965).

BP6

Variant X-15628116-T-C is Benign according to our data. Variant chrX-15628116-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2461903.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020665.6. 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
	CLTRN	NM_020665.6	MANE Select	c.524A>G	p.Glu175Gly	missense	Exon 6 of 6	NP_065716.1	Q9HBJ8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLTRN	ENST00000380342.4	TSL:1 MANE Select	c.524A>G	p.Glu175Gly	missense	Exon 6 of 6	ENSP00000369699.3	Q9HBJ8
ENSG00000285602	ENST00000649243.1		n.356+11446A>G		intron	N/A	ENSP00000497489.1	A0A3B3IT09
CLTRN	ENST00000918250.1		c.524A>G	p.Glu175Gly	missense	Exon 7 of 7	ENSP00000588309.1

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111923

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000821

AC:

AN:

121840

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000100

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000255

AC:

AN:

979136

Hom.:

Cov.:

AF XY:

0.0000267

AC XY:

AN XY:

299608

show subpopulations

African (AFR)

AF:

0.0000890

AC:

AN:

22462

American (AMR)

AF:

0.00

AC:

AN:

22803

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15461

East Asian (EAS)

AF:

0.00

AC:

AN:

26191

South Asian (SAS)

AF:

0.00

AC:

AN:

33685

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3658

European-Non Finnish (NFE)

AF:

0.0000283

AC:

AN:

778030

Other (OTH)

AF:

0.0000247

AC:

AN:

40420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000536

AC:

AN:

111975

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34141

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30838

American (AMR)

AF:

0.00

AC:

AN:

10514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3569

South Asian (SAS)

AF:

0.00

AC:

AN:

2670

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6113

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000752

AC:

AN:

53211

Other (OTH)

AF:

0.000664

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000142

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.1

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.13

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.48

M_CAP

Benign

0.030

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.89

PhyloP100

-1.2

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.060

REVEL

Benign

0.12

Sift

Benign

0.47

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.050

MutPred

0.35

Loss of solvent accessibility (P = 0.0387)

MVP

0.29

MPC

0.011

ClinPred

0.0055

GERP RS

-2.7

Varity_R

0.031

gMVP

0.16

Mutation Taster

=94/6

polymorphism

(source)

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

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