rs11549950

Variant names:

• chr12-52515133-T-A
• NM_000424.4:c.1582A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-52515133-T-A
• chr12-52515133-T-C

Variant summary

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

The NM_000424.4(KRT5):​c.1582A>T​(p.Ser528Cys) 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 1,459,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRT5 NM_000424.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

Genes affected

KRT5 (HGNC:6442): (keratin 5) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the basal layer of the epidermis with family member KRT14. Mutations in these genes have been associated with a complex of diseases termed epidermolysis bullosa simplex. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [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=0.1293005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT5	NM_000424.4	c.1582A>T	p.Ser528Cys	missense_variant	Exon 9 of 9	ENST00000252242.9	NP_000415.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT5	ENST00000252242.9	c.1582A>T	p.Ser528Cys	missense_variant	Exon 9 of 9	1	NM_000424.4	ENSP00000252242.4
KRT5	ENST00000549511.5	n.789A>T		non_coding_transcript_exon_variant	Exon 5 of 5	2
KRT5	ENST00000552952.1	n.507A>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459376 Hom.: 0 Cov.: 36 AF XY: 0.00000276 AC XY: 2 AN XY: 725810

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.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	4.4
DANN	Benign	0.88
DEOGEN2	Benign	0.35	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.39
Sift	Benign	0.085	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.46	P
Vest4		0.26
MutPred		0.26		Loss of phosphorylation at S528 (P = 0.0059);
MVP		0.41
MPC		0.21
ClinPred		0.18	T
GERP RS		0.084
Varity_R		0.064
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-52908917;