X-9967920-C-T

Variant names:

• chrX-9967920-C-T
• rs2084913091
• NM_001195081.2:c.563C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001195081.2(CLDN34):​c.563C>T​(p.Pro188Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,040,484 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000011 (0 hom. 6 hem.)
• Consequence: CLDN34 NM_001195081.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17
• Publications: 0 publications found

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]

ENSG00000310579 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.071321934).
• BP6: Variant X-9967920-C-T is Benign according to our data. Variant chrX-9967920-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3493429.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 6 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.563C>T	p.Pro188Leu	missense	Exon 1 of 1	NP_001182010.1	H7C241

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN34	ENST00000445307.4	TSL:6 MANE Select	c.563C>T	p.Pro188Leu	missense	Exon 1 of 1	ENSP00000403980.3	H7C241
	ENSG00000310579	ENST00000850985.1		c.5168C>T	p.Pro1723Leu	missense	Exon 10 of 10	ENSP00000521067.1
	CLDN34	ENST00000850986.1		c.563C>T	p.Pro188Leu	missense	Exon 2 of 2	ENSP00000521068.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.0000106 AC: 11 AN: 1040484 Hom.: 0 Cov.: 30 AF XY: 0.0000177 AC XY: 6 AN XY: 339560

African (AFR) AF: 0.00 AC: 0 AN: 24883

American (AMR) AF: 0.00 AC: 0 AN: 27909

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18627

East Asian (EAS) AF: 0.0000369 AC: 1 AN: 27129

South Asian (SAS) AF: 0.00 AC: 0 AN: 49850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25901

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4082

European-Non Finnish (NFE) AF: 0.0000122 AC: 10 AN: 817852

Other (OTH) AF: 0.00 AC: 0 AN: 44251

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.080
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.035
DANN	Benign	0.21
DEOGEN2	Benign	0.0039	T
FATHMM_MKL	Benign	0.00052	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.95	T
PhyloP100		1.2
PrimateAI	Benign	0.19	T
REVEL	Benign	0.072
Sift4G	Benign	1.0	T
Vest4		0.094
MVP		0.21
ClinPred		0.022	T
GERP RS		1.0
Varity_R		0.051
gMVP		0.63

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: rs2084913091; hg19: chrX-9935960;