rs746058489

Variant names:

• chr19-35487747-T-C
• rs746058489
• NM_207392.3:c.226A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-35487747-T-C
• chr19-35487747-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207392.3(KRTDAP):​c.226A>G​(p.Lys76Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRTDAP NM_207392.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.911

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11636412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTDAP	NM_207392.3	c.226A>G	p.Lys76Glu	missense_variant	Exon 5 of 6	ENST00000338897.4	NP_997275.1
KRTDAP	NM_001244847.2	c.184A>G	p.Lys62Glu	missense_variant	Exon 4 of 5		NP_001231776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTDAP	ENST00000338897.4	c.226A>G	p.Lys76Glu	missense_variant	Exon 5 of 6	1	NM_207392.3	ENSP00000339251.3
KRTDAP	ENST00000484218.6	c.184A>G	p.Lys62Glu	missense_variant	Exon 4 of 5	2		ENSP00000470713.1
KRTDAP	ENST00000479340.1	n.307A>G		non_coding_transcript_exon_variant	Exon 5 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251402 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135870

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461092 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726944

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	0.0092	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.11
Sift	Benign	0.25	.;T
Sift4G	Benign	0.15	T;T
Polyphen		0.56	.;P
Vest4		0.37
MutPred		0.28		.;Loss of methylation at K76 (P = 0.0145);
MVP		0.099
MPC		0.64
ClinPred		0.96	D
GERP RS		3.4
Varity_R		0.077
gMVP		0.11

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: rs746058489; hg19: chr19-35978649;