rs147410947

Variant names:

• chr3-98516669-C-A
• rs147410947
• NM_001040181.2:c.752G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-98516669-C-A
• chr3-98516669-C-G
• chr3-98516669-C-T

Variant summary

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

The NM_001040181.2(CLDND1):​c.752G>T​(p.Arg251Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R251P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CLDND1 NM_001040181.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63
• Publications: 2 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 2 ACMG points.

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

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.752G>T	p.Arg251Leu	missense	Exon 5 of 5	NP_001035271.1	Q9NY35-1
	CLDND1	NM_001040182.2		c.821G>T	p.Arg274Leu	missense	Exon 6 of 6	NP_001035272.1	A0A0R4J2F2
	CLDND1	NM_001040183.2		c.752G>T	p.Arg251Leu	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.752G>T	p.Arg251Leu	missense	Exon 5 of 5	ENSP00000340247.6	Q9NY35-1
	CLDND1	ENST00000394181.6	TSL:1	c.821G>T	p.Arg274Leu	missense	Exon 6 of 6	ENSP00000377735.3	A0A0R4J2F2
	CLDND1	ENST00000394180.6	TSL:1	c.752G>T	p.Arg251Leu	missense	Exon 6 of 6	ENSP00000377734.2	Q9NY35-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251174 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461722 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727152

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111922

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.6
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.78	P
Vest4		0.60
MutPred		0.65		Loss of MoRF binding (P = 2e-04)
MVP		0.25
ClinPred		0.97	D
GERP RS		5.2
PromoterAI		-0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.68
Mutation Taster		=59/41	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: rs147410947; hg19: chr3-98235513;