Genetic Variant NM_001195081.2:c.410C>T (chrX-9967767-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001195081.2(CLDN34):c.410C>T(p.Ala137Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000893 in 1,153,495 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000088 ( 0 hom. 28 hem. )

Consequence

CLDN34
NM_001195081.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

Publications

0 publications found

Variant links:

Genes affected

CLDN34 (HGNC:51259): (claudin 34) Predicted to enable structural molecule activity. Predicted to be involved in bicellular tight junction assembly and cell adhesion. Predicted to be integral component of membrane. Predicted to be active in bicellular tight junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLDN34 links:

ENSG00000310579 (HGNC:):

ENSG00000310579 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26293206).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195081.2. 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
	CLDN34	NM_001195081.2	MANE Select	c.410C>T	p.Ala137Val	missense	Exon 1 of 1	NP_001182010.1	H7C241

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLDN34	ENST00000445307.4	TSL:6 MANE Select	c.410C>T	p.Ala137Val	missense	Exon 1 of 1	ENSP00000403980.3	H7C241
ENSG00000310579	ENST00000850985.1		c.5015C>T	p.Ala1672Val	missense	Exon 10 of 10	ENSP00000521067.1
CLDN34	ENST00000850986.1		c.410C>T	p.Ala137Val	missense	Exon 2 of 2	ENSP00000521068.1

Frequencies

GnomAD3 genomes

AF:

0.0000984

AC:

AN:

111745

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000976

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:

0.000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000307

AC:

AN:

97768

AF XY:

0.0000274

show subpopulations

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:

0.0000523

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000883

AC:

AN:

1041750

Hom.:

Cov.:

AF XY:

0.0000822

AC XY:

AN XY:

340782

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24903

American (AMR)

AF:

0.00

AC:

AN:

27909

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18639

East Asian (EAS)

AF:

0.00

AC:

AN:

27132

South Asian (SAS)

AF:

0.00

AC:

AN:

49873

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4088

European-Non Finnish (NFE)

AF:

0.0000989

AC:

AN:

819010

Other (OTH)

AF:

0.000248

AC:

AN:

44294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000984

AC:

AN:

111745

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

33911

show subpopulations

African (AFR)

AF:

0.0000976

AC:

AN:

30749

American (AMR)

AF:

0.00

AC:

AN:

10473

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3567

South Asian (SAS)

AF:

0.00

AC:

AN:

2661

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6031

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000150

AC:

AN:

53195

Other (OTH)

AF:

0.00

AC:

AN:

1498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.553

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

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

0.29

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.39

MetaRNN

Benign

0.26

MetaSVM

Uncertain

-0.15

PhyloP100

3.3

PrimateAI

Benign

0.27

REVEL

Benign

0.10

Sift4G

Uncertain

0.014

Vest4

0.39

MVP

0.11

ClinPred

0.86

GERP RS

3.8

PromoterAI

0.00090

Neutral

(source)

Varity_R

0.088

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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