7-101232656-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014343.3(CLDN15):​c.529C>T​(p.Leu177Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 1,587,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (0 hom.)
• Consequence: CLDN15 NM_014343.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14662594).

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>T	p.Leu177Phe	missense	Exon 4 of 5	NP_055158.1	P56746
	CLDN15	NM_001185080.2		c.529C>T	p.Leu177Phe	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>T	p.Leu177Phe	missense	Exon 4 of 5	ENSP00000308870.5	P56746
	CLDN15	ENST00000401528.5	TSL:2	c.529C>T	p.Leu177Phe	missense	Exon 5 of 6	ENSP00000385300.1	P56746
	CLDN15	ENST00000412417.1	TSL:5	c.460C>T	p.Leu154Phe	missense	Exon 4 of 4	ENSP00000390230.1	C9JHQ4

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000117 AC: 23 AN: 195802 AF XY: 0.000150

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: 0.000265

Gnomad OTH exome AF: 0.000198

GnomAD4 exome AF: 0.000460 AC: 660 AN: 1434870 Hom.: 0 Cov.: 32 AF XY: 0.000460 AC XY: 327 AN XY: 711558

African (AFR) AF: 0.000121 AC: 4 AN: 33076

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

Ashkenazi Jewish (ASJ) AF: 0.0000393 AC: 1 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: 0.000588 AC: 646 AN: 1099166

Other (OTH) AF: 0.000152 AC: 9 AN: 59290

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74346

African (AFR) AF: 0.000121 AC: 5 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000379 Hom.: 0

Bravo AF: 0.000230

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000357 AC: 3

ExAC AF: 0.0000670 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.15
DANN	Benign	0.97
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.78	N
PhyloP100		-0.65
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.24
Sift	Benign	0.24	T
Sift4G	Benign	0.50	T
Polyphen		0.24	B
Vest4		0.21
MVP		0.77
MPC		0.35
ClinPred		0.039	T
GERP RS		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.048
gMVP		0.37
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs372104568; hg19: chr7-100875937;