12-52807202-C-A

Position:

• chr12-52807202-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002272.4(KRT4):​c.1430G>T​(p.Gly477Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRT4 NM_002272.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.75

Genes affected

KRT4 (HGNC:6441): (keratin 4) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in differentiated layers of the mucosal and esophageal epithelia with family member KRT13. Mutations in these genes have been associated with White Sponge Nevus, characterized by oral, esophageal, and anal leukoplakia. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT4	NM_002272.4	c.1430G>T	p.Gly477Val	missense_variant	9/9	ENST00000551956.2	NP_002263.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT4	ENST00000551956.2	c.1430G>T	p.Gly477Val	missense_variant	9/9	1	NM_002272.4	ENSP00000448220.1
KRT4	ENST00000548097.5	n.*942G>T		non_coding_transcript_exon_variant	9/9	1		ENSP00000449755.1
KRT4	ENST00000548097.5	n.*942G>T		3_prime_UTR_variant	9/9	1		ENSP00000449755.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

KRT4-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 11, 2024

The KRT4 c.1430G>T variant is predicted to result in the amino acid substitution p.Gly477Val. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	17
DANN	Benign	0.89
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.15	N
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	0.79	D
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.033	D
Vest4		0.46
MVP		0.85
MPC		0.20
ClinPred		0.32	T
GERP RS		2.3
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-53200986;