19-35490370-G-A

Variant names:

• chr19-35490370-G-A
• rs146235027
• NM_207392.3:c.73C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_207392.3(KRTDAP):​c.73C>T​(p.Leu25Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KRTDAP NM_207392.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=1.88 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207392.3. 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
	KRTDAP	NM_207392.3	MANE Select	c.73C>T	p.Leu25Leu	synonymous	Exon 1 of 6	NP_997275.1	P60985-1
	KRTDAP	NM_001244847.2		c.73C>T	p.Leu25Leu	synonymous	Exon 1 of 5	NP_001231776.1	P60985-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTDAP	ENST00000338897.4	TSL:1 MANE Select	c.73C>T	p.Leu25Leu	synonymous	Exon 1 of 6	ENSP00000339251.3	P60985-1
	KRTDAP	ENST00000484218.6	TSL:2	c.73C>T	p.Leu25Leu	synonymous	Exon 1 of 5	ENSP00000470713.1	P60985-2
	KRTDAP	ENST00000479340.1	TSL:2	n.169-1530C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 249760 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.0
DANN	Benign	0.61
PhyloP100		1.9
PromoterAI		0.00040	Neutral

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

Other links and lift over

dbSNP: rs146235027; hg19: chr19-35981272;