19-7925472-C-T

Variant names:

• chr19-7925472-C-T
• rs1983755893
• NM_206833.4:c.67G>A

Variant summary

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

The NM_206833.4(CTXN1):​c.67G>A​(p.Gly23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000071 in 1,408,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: CTXN1 NM_206833.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37
• Publications: 0 publications found

Genes affected

CTXN1 (HGNC:31108): (cortexin 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC124904629 (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=0.12792647).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206833.4. 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
	CTXN1	NM_206833.4	MANE Select	c.67G>A	p.Gly23Ser	missense	Exon 2 of 2	NP_996664.1	P60606

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTXN1	ENST00000318978.6	TSL:1 MANE Select	c.67G>A	p.Gly23Ser	missense	Exon 2 of 2	ENSP00000313226.3	P60606

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000710 AC: 10 AN: 1408060 Hom.: 0 Cov.: 34 AF XY: 0.00000429 AC XY: 3 AN XY: 700092

African (AFR) AF: 0.00 AC: 0 AN: 29780

American (AMR) AF: 0.00 AC: 0 AN: 40050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24900

East Asian (EAS) AF: 0.00 AC: 0 AN: 35112

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5620

European-Non Finnish (NFE) AF: 0.00000824 AC: 9 AN: 1092844

Other (OTH) AF: 0.00 AC: 0 AN: 58460

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.084
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.081
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	0.99	T
Polyphen		0.18	B
Vest4		0.12
MutPred		0.17		Gain of glycosylation at G23 (P = 0.0123)
MVP		0.23
MPC		2.4
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.21
gMVP		0.67
Mutation Taster		=85/15	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

dbSNP: rs1983755893; hg19: chr19-7990357;