chr6-155276174-T-C

Position:

• chr6-155276174-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001001346.3(CLDN20):​c.455T>C​(p.Val152Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLDN20 NM_001001346.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86

Genes affected

CLDN20 (HGNC:2042): (claudin 20) 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. [provided by RefSeq, Jun 2010]

TFB1M (HGNC:17037): (transcription factor B1, mitochondrial) The protein encoded by this gene is a dimethyltransferase that methylates the conserved stem loop of mitochondrial 12S rRNA. The encoded protein also is part of the basal mitochondrial transcription complex and is necessary for mitochondrial gene expression. The methylation and transcriptional activities of this protein are independent of one another. Variations in this gene may influence the severity of aminoglycoside-induced deafness (AID).[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3361699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN20	NM_001001346.3	c.455T>C	p.Val152Ala	missense_variant	2/2	ENST00000367165.3	NP_001001346.1
TFB1M	NM_016020.4	c.666+8984A>G		intron_variant		ENST00000367166.5	NP_057104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN20	ENST00000367165.3	c.455T>C	p.Val152Ala	missense_variant	2/2	1	NM_001001346.3	ENSP00000356133	P1
TFB1M	ENST00000367166.5	c.666+8984A>G		intron_variant		1	NM_016020.4	ENSP00000356134	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.455T>C (p.V152A) alteration is located in exon 2 (coding exon 1) of the CLDN20 gene. This alteration results from a T to C substitution at nucleotide position 455, causing the valine (V) at amino acid position 152 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	-0.071	T
MutationAssessor	Benign	0.17	N
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.56
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.028	D
Polyphen		0.81	P
Vest4		0.13
MutPred		0.52		Gain of disorder (P = 0.0397);
MVP		0.85
MPC		0.026
ClinPred		0.89	D
GERP RS		4.5
Varity_R		0.16
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs1485405144; hg19: chr6-155597308;