3-98516745-G-C

Position:

• chr3-98516745-G-C

Variant summary

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

The NM_001040181.2(CLDND1):​c.676C>G​(p.Gln226Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLDND1 NM_001040181.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.29

Genes affected

CLDND1 (HGNC:1322): (claudin domain containing 1) Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

CLDND1 (HGNC:):

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
CLDND1	NM_001040181.2	c.676C>G	p.Gln226Glu	missense_variant	5/5	ENST00000341181.11	NP_001035271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDND1	ENST00000341181.11	c.676C>G	p.Gln226Glu	missense_variant	5/5	1	NM_001040181.2	ENSP00000340247.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Nov 10, 2024

The c.745C>G (p.Q249E) alteration is located in exon 6 (coding exon 6) of the CLDND1 gene. This alteration results from a C to G substitution at nucleotide position 745, causing the glutamine (Q) at amino acid position 249 to be replaced by a glutamic acid (E). 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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;T;T;T;T;T;.;T;T;.;.;T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;.;.;.;D;.;D;.;D;D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.1	M;M;M;M;.;M;.;M;.;.;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.85	N;N;N;N;.;N;N;N;N;N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.19	T;T;T;T;.;T;T;T;T;T;T;T;T
Sift4G	Benign	0.36	T;T;T;T;T;T;T;T;.;.;.;.;.
Polyphen		0.89	P;P;P;P;.;P;.;P;.;P;.;.;.
Vest4		0.61
MutPred		0.50		Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);.;Gain of loop (P = 0.0502);.;Gain of loop (P = 0.0502);.;Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);.;Gain of loop (P = 0.0502);
MVP		0.54
ClinPred		0.71	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr3-98235589;