NM_001001346.3:c.16C>T

Variant names:

• chr6-155275735-C-T
• NM_001001346.3:c.16C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001001346.3(CLDN20):​c.16C>T​(p.Leu6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 1.64
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41997516).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001346.3. 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
	CLDN20	NM_001001346.3	MANE Select	c.16C>T	p.Leu6Phe	missense	Exon 2 of 2	NP_001001346.1	P56880
	TFB1M	NM_016020.4	MANE Select	c.666+9423G>A		intron	N/A	NP_057104.2	E5KTM5
	TFB1M	NM_001350501.2		c.666+9423G>A		intron	N/A	NP_001337430.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN20	ENST00000367165.3	TSL:1 MANE Select	c.16C>T	p.Leu6Phe	missense	Exon 2 of 2	ENSP00000356133.3	P56880
	TFB1M	ENST00000367166.5	TSL:1 MANE Select	c.666+9423G>A		intron	N/A	ENSP00000356134.4	Q8WVM0
	CLDN20	ENST00000909656.1		c.16C>T	p.Leu6Phe	missense	Exon 2 of 2	ENSP00000579715.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	0.10
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.086
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	0.44	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.6
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.098
MutPred		0.64		Gain of glycosylation at S3 (P = 0.096)
MVP		0.91
MPC		0.036
ClinPred		0.97	D
GERP RS		2.7
Varity_R		0.23
gMVP		0.61
Mutation Taster		=88/12	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

hg19: chr6-155596869;