7-101232656-G-C

Variant names:

• chr7-101232656-G-C
• rs372104568
• NM_014343.3:c.529C>G

Variant summary

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

The NM_014343.3(CLDN15):​c.529C>G​(p.Leu177Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 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. L177F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CLDN15 NM_014343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654
• Publications: 0 publications found

Genes affected

CLDN15 (HGNC:2036): (claudin 15) This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2010]

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=0.12325114).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014343.3. 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
	CLDN15	NM_014343.3	MANE Select	c.529C>G	p.Leu177Val	missense	Exon 4 of 5	NP_055158.1	P56746
	CLDN15	NM_001185080.2		c.529C>G	p.Leu177Val	missense	Exon 5 of 6	NP_001172009.1	P56746

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN15	ENST00000308344.10	TSL:1 MANE Select	c.529C>G	p.Leu177Val	missense	Exon 4 of 5	ENSP00000308870.5	P56746
	CLDN15	ENST00000401528.5	TSL:2	c.529C>G	p.Leu177Val	missense	Exon 5 of 6	ENSP00000385300.1	P56746
	CLDN15	ENST00000412417.1	TSL:5	c.460C>G	p.Leu154Val	missense	Exon 4 of 4	ENSP00000390230.1	C9JHQ4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434870 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 711558

African (AFR) AF: 0.00 AC: 0 AN: 33076

American (AMR) AF: 0.00 AC: 0 AN: 39772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25456

East Asian (EAS) AF: 0.00 AC: 0 AN: 38540

South Asian (SAS) AF: 0.00 AC: 0 AN: 83366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1099166

Other (OTH) AF: 0.00 AC: 0 AN: 59290

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.0090
DANN	Benign	0.75
DEOGEN2	Benign	0.32	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.17	N
PhyloP100		-0.65
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.26
Sift	Benign	1.0	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.55		Gain of sheet (P = 0.0344)
MVP		0.65
MPC		0.33
ClinPred		0.021	T
GERP RS		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.032
gMVP		0.27
Mutation Taster		=88/12	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: rs372104568; hg19: chr7-100875937;