NM_001040181.2:c.745G>C

Variant names:

• chr3-98516676-C-G
• NM_001040181.2:c.745G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040181.2(CLDND1):​c.745G>C​(p.Ala249Pro) 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 (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLDND1 NM_001040181.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.33
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39813542).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040181.2. 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
	CLDND1	NM_001040181.2	MANE Select	c.745G>C	p.Ala249Pro	missense	Exon 5 of 5	NP_001035271.1	Q9NY35-1
	CLDND1	NM_001040182.2		c.814G>C	p.Ala272Pro	missense	Exon 6 of 6	NP_001035272.1	A0A0R4J2F2
	CLDND1	NM_001040183.2		c.745G>C	p.Ala249Pro	missense	Exon 5 of 5	NP_001035273.1	Q9NY35-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDND1	ENST00000341181.11	TSL:1 MANE Select	c.745G>C	p.Ala249Pro	missense	Exon 5 of 5	ENSP00000340247.6	Q9NY35-1
	CLDND1	ENST00000394181.6	TSL:1	c.814G>C	p.Ala272Pro	missense	Exon 6 of 6	ENSP00000377735.3	A0A0R4J2F2
	CLDND1	ENST00000394180.6	TSL:1	c.745G>C	p.Ala249Pro	missense	Exon 6 of 6	ENSP00000377734.2	Q9NY35-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.3
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.61		Loss of helix (P = 0.0033)
MVP		0.16
ClinPred		0.97	D
GERP RS		6.0
PromoterAI		0.0014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.86
Mutation Taster		=14/86	disease causing

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: chr3-98235520;