Genetic Variant NM_014343.3:c.314T>C (chr7-101234346-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_014343.3(CLDN15):c.314T>C(p.Ile105Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000354 in 1,612,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CLDN15
NM_014343.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

Publications

0 publications found

Variant links:

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]

CLDN15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19116583).

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.314T>C	p.Ile105Thr	missense	Exon 2 of 5	NP_055158.1	P56746
	CLDN15	NM_001185080.2		c.314T>C	p.Ile105Thr	missense	Exon 3 of 6	NP_001172009.1	P56746

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLDN15	ENST00000308344.10	TSL:1 MANE Select	c.314T>C	p.Ile105Thr	missense	Exon 2 of 5	ENSP00000308870.5	P56746
CLDN15	ENST00000433422.1	TSL:1	n.638T>C		non_coding_transcript_exon	Exon 3 of 3
CLDN15	ENST00000463331.5	TSL:1	n.623T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000759

AC:

AN:

250178

AF XY:

0.0000591

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000336

AC:

AN:

1460252

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.000112

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.000302

AC:

AN:

39698

South Asian (SAS)

AF:

0.000174

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52168

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111668

Other (OTH)

AF:

0.0000497

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41456

American (AMR)

AF:

0.000131

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000195

AC:

AN:

5130

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67964

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000166

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.82

Eigen

Benign

0.0044

Eigen_PC

Benign

-0.091

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.71

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.19

MetaSVM

Uncertain

0.16

MutationAssessor

Uncertain

2.0

PhyloP100

3.9

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.55

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

0.65

Vest4

0.60

MVP

0.92

MPC

0.84

ClinPred

0.23

GERP RS

5.3

Varity_R

0.34

gMVP

0.79

Mutation Taster

=90/10

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over