19-35490412-G-A

Variant names:

• chr19-35490412-G-A
• NM_207392.3:c.31C>T

Variant summary

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

The NM_207392.3(KRTDAP):​c.31C>T​(p.Leu11Phe) 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 (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KRTDAP NM_207392.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75

Genes affected

KRTDAP (HGNC:16313): (keratinocyte differentiation associated protein) This gene encodes a protein which may function in the regulation of keratinocyte differentiation and maintenance of stratified epithelia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

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 rank	MANE	Protein	UniProt
KRTDAP	NM_207392.3	c.31C>T	p.Leu11Phe	missense_variant	Exon 1 of 6	ENST00000338897.4	NP_997275.1
KRTDAP	NM_001244847.2	c.31C>T	p.Leu11Phe	missense_variant	Exon 1 of 5		NP_001231776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTDAP	ENST00000338897.4	c.31C>T	p.Leu11Phe	missense_variant	Exon 1 of 6	1	NM_207392.3	ENSP00000339251.3
KRTDAP	ENST00000484218.6	c.31C>T	p.Leu11Phe	missense_variant	Exon 1 of 5	2		ENSP00000470713.1
KRTDAP	ENST00000479340.1	n.169-1572C>T		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.31C>T (p.L11F) alteration is located in exon 1 (coding exon 1) of the KRTDAP gene. This alteration results from a C to T substitution at nucleotide position 31, causing the leucine (L) at amino acid position 11 to be replaced by a phenylalanine (F). 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	0.13
BayesDel_addAF	Benign	-0.0079	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.080
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.86	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.9	.;D
REVEL	Benign	0.099
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.56
MutPred		0.28		Gain of catalytic residue at L11 (P = 0.0154);Gain of catalytic residue at L11 (P = 0.0154);
MVP		0.31
MPC		0.56
ClinPred		0.96	D
GERP RS		3.9
Varity_R		0.61
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35981314;