NM_000421.5:c.1703C>A

Variant names:

• chr17-40818832-G-T
• NM_000421.5:c.1703C>A

Variant summary

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

The NM_000421.5(KRT10):​c.1703C>A​(p.Ser568Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000904 in 1,105,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 28)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: KRT10 NM_000421.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381

Genes affected

KRT10 (HGNC:6413): (keratin 10) This gene encodes a member of the type I (acidic) cytokeratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. Mutations in this gene are associated with epidermolytic hyperkeratosis. This gene is located within a cluster of keratin family members on chromosome 17q21. [provided by RefSeq, Jul 2008]

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=0.13452125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT10	NM_000421.5	c.1703C>A	p.Ser568Tyr	missense_variant	Exon 7 of 8	ENST00000269576.6	NP_000412.4
KRT10	NM_001379366.1	c.1703C>A	p.Ser568Tyr	missense_variant	Exon 7 of 8		NP_001366295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6	c.1703C>A	p.Ser568Tyr	missense_variant	Exon 7 of 8	1	NM_000421.5	ENSP00000269576.5
KRT10	ENST00000635956.2	c.1703C>A	p.Ser568Tyr	missense_variant	Exon 7 of 8	2		ENSP00000490524.2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 9.04e-7 AC: 1 AN: 1105920 Hom.: 0 Cov.: 30 AF XY: 0.00000179 AC XY: 1 AN XY: 557812

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000466

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Benign	0.79
DEOGEN2	Benign	0.069	T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.28	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.19	.;N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	.;D
Sift4G	Uncertain	0.026	.;D
Polyphen		0.79	.;P
Vest4		0.37
MutPred		0.33		.;Gain of sheet (P = 0.0149);
MVP		0.80
MPC		0.54
ClinPred		0.33	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-38975084;