5-127657703-C-A

Position:

• chr5-127657703-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001048252.3(CTXN3):​c.182C>A​(p.Thr61Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTXN3 NM_001048252.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56

Genes affected

CTXN3 (HGNC:31110): (cortexin 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35211903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTXN3	NM_001048252.3	c.182C>A	p.Thr61Asn	missense_variant	3/3	ENST00000379445.8	NP_001041717.1
LOC105379164	XR_002956226.1	n.140-5342G>T		intron_variant, non_coding_transcript_variant
CTXN3	NM_001127385.2	c.182C>A	p.Thr61Asn	missense_variant	3/3		NP_001120857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTXN3	ENST00000379445.8	c.182C>A	p.Thr61Asn	missense_variant	3/3	1	NM_001048252.3	ENSP00000368758	P1
CTXN3	ENST00000395322.3	c.182C>A	p.Thr61Asn	missense_variant	3/3	1		ENSP00000378732	P1
	ENST00000512352.1	n.310-5342G>T		intron_variant, non_coding_transcript_variant		5
CTXN3	ENST00000620385.1	c.182C>A	p.Thr61Asn	missense_variant	1/1			ENSP00000482081	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2024

The c.182C>A (p.T61N) alteration is located in exon 3 (coding exon 1) of the CTXN3 gene. This alteration results from a C to A substitution at nucleotide position 182, causing the threonine (T) at amino acid position 61 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	.;.;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.1	N;N;.
REVEL	Benign	0.16
Sift	Uncertain	0.014	D;D;.
Sift4G	Uncertain	0.037	D;D;D
Polyphen		0.96	D;D;D
Vest4		0.32
MutPred		0.11		Gain of disorder (P = 0.1756);Gain of disorder (P = 0.1756);Gain of disorder (P = 0.1756);
MVP		0.13
MPC		0.83
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-126993395; COSMIC: COSV65217943; COSMIC: COSV65217943;