18-74559437-G-T

Position:

• chr18-74559437-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032649.6(CNDP1):​c.268G>T​(p.Ala90Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNDP1 NM_032649.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62

Genes affected

CNDP1 (HGNC:20675): (carnosine dipeptidase 1) This gene encodes a member of the M20 metalloprotease family. The encoded protein is specifically expressed in the brain, is a homodimeric dipeptidase which was identified as human carnosinase. This gene contains trinucleotide (CTG) repeat length polymorphism in the coding region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNDP1	NM_032649.6	c.268G>T	p.Ala90Ser	missense_variant	3/12	ENST00000358821.8	NP_116038.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNDP1	ENST00000358821.8	c.268G>T	p.Ala90Ser	missense_variant	3/12	1	NM_032649.6	ENSP00000351682.3
CNDP1	ENST00000582365.1	c.139G>T	p.Ala47Ser	missense_variant	2/11	5		ENSP00000462096.1
CNDP1	ENST00000585136.1	n.433G>T		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459394 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jul 09, 2021

The c.268G>T (p.A90S) alteration is located in exon 3 (coding exon 3) of the CNDP1 gene. This alteration results from a G to T substitution at nucleotide position 268, causing the alanine (A) at amino acid position 90 to be replaced by a serine (S). 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	Benign	0.19
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	.;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.72	.;T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.25
Sift	Benign	0.042	D;.
Sift4G	Benign	0.081	T;T
Vest4		0.34
MutPred		0.42		Gain of phosphorylation at A90 (P = 0.0276);.;
MVP		0.56
MPC		0.60
ClinPred		0.97	D
GERP RS		5.4
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-72226672; COSMIC: COSV100722481; COSMIC: COSV100722481;