rs779936319

Variant names:

• chr17-41582448-C-A
• NM_000526.5:c.1406G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41582448-C-A
• chr17-41582448-C-T

Variant summary

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

The NM_000526.5(KRT14):​c.1406G>T​(p.Arg469Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R469H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: KRT14 NM_000526.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

Genes affected

KRT14 (HGNC:6416): (keratin 14) This gene encodes a member of the keratin family, the most diverse group of intermediate filaments. This gene product, a type I keratin, is usually found as a heterotetramer with two keratin 5 molecules, a type II keratin. Together they form the cytoskeleton of epithelial cells. Mutations in the genes for these keratins are associated with epidermolysis bullosa simplex. At least one pseudogene has been identified at 17p12-p11. [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=0.18685687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT14	NM_000526.5	c.1406G>T	p.Arg469Leu	missense_variant	Exon 8 of 8	ENST00000167586.7	NP_000517.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT14	ENST00000167586.7	c.1406G>T	p.Arg469Leu	missense_variant	Exon 8 of 8	1	NM_000526.5	ENSP00000167586.6
KRT14	ENST00000441550.2	n.914G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1413596 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 698658

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: 9.20e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T
Eigen	Benign	0.0018
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.28	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.40
Sift	Benign	0.057	T
Sift4G	Uncertain	0.026	D
Polyphen		0.062	B
Vest4		0.28
MutPred		0.39		Loss of MoRF binding (P = 0);
MVP		0.88
MPC		0.61
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.33
gMVP		0.88

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: chr17-39738700;