NM_020665.6:c.130A>G

Variant names:

• chrX-15659089-T-C
• NM_020665.6:c.130A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020665.6(CLTRN):​c.130A>G​(p.Thr44Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: CLTRN NM_020665.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.419
• Publications: 0 publications found

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

ENSG00000285602 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08915576).

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.130A>G	p.Thr44Ala	missense	Exon 3 of 6	NP_065716.1	Q9HBJ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLTRN	ENST00000380342.4	TSL:1 MANE Select	c.130A>G	p.Thr44Ala	missense	Exon 3 of 6	ENSP00000369699.3	Q9HBJ8
	ENSG00000285602	ENST00000649243.1		n.-27A>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 20	ENSP00000497489.1	A0A3B3IT09
	ENSG00000285602	ENST00000649243.1		n.-27A>G		non_coding_transcript_exon	Exon 3 of 20	ENSP00000497489.1	A0A3B3IT09

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 21

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.71
DANN	Benign	0.55
DEOGEN2	Benign	0.080	T
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.91	T
PhyloP100		0.42
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.20
Sift	Benign	0.74	T
Sift4G	Benign	0.80	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.19		Loss of sheet (P = 0.1158)
MVP		0.36
MPC		0.011
ClinPred		0.029	T
GERP RS		-2.9
Varity_R		0.034
gMVP		0.11
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chrX-15677212;