Genetic Variant CLTRN:p.Asn45Ser (chrX-15659085-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_020665.6(CLTRN):c.134A>G(p.Asn45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,053,082 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 0.0000019 ( 0 hom. 2 hem. )

Consequence

CLTRN
NM_020665.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.251

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.147493).

BP6

Variant X-15659085-T-C is Benign according to our data. Variant chrX-15659085-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3834233.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 2 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.134A>G	p.Asn45Ser	missense	Exon 3 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.134A>G	p.Asn45Ser	missense	Exon 3 of 6	ENSP00000369699.3	Q9HBJ8
ENSG00000285602	ENST00000649243.1		n.-23A>G		non_coding_transcript_exon	Exon 3 of 20	ENSP00000497489.1	A0A3B3IT09
ENSG00000285602	ENST00000649243.1		n.-23A>G		5_prime_UTR	Exon 3 of 20	ENSP00000497489.1	A0A3B3IT09

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000190

AC:

AN:

1053082

Hom.:

Cov.:

AF XY:

0.00000611

AC XY:

AN XY:

327136

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25377

American (AMR)

AF:

0.00

AC:

AN:

34369

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18300

East Asian (EAS)

AF:

0.0000351

AC:

AN:

28461

South Asian (SAS)

AF:

0.00

AC:

AN:

52986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38093

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3958

European-Non Finnish (NFE)

AF:

0.00000124

AC:

AN:

807774

Other (OTH)

AF:

0.00

AC:

AN:

43764

Age Distribution

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

Cov.:

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

0.060

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.5

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.40

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.71

M_CAP

Benign

0.051

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.67

PhyloP100

0.25

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.24

Sift

Benign

0.24

Sift4G

Benign

0.28

Polyphen

0.031

Vest4

0.19

MutPred

0.34

Gain of phosphorylation at T44 (P = 0.1373)

MVP

0.30

MPC

0.011

ClinPred

0.42

GERP RS

3.3

Varity_R

0.12

gMVP

0.29

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over