rs12312467

Positions:

• chr12-52790941-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_057088.3(KRT3):​c.1536-69C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 1,449,242 control chromosomes in the GnomAD database, including 8,611 homozygotes. 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: 𝑓 0.079 (1304 hom., cov: 33)
  • Exomes 𝑓: 0.058 (7307 hom.)
• Consequence: KRT3 NM_057088.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

Genes affected

KRT3 (HGNC:6440): (keratin 3) 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 corneal epithelium with family member KRT12 and mutations in these genes have been associated with Meesmann's Corneal Dystrophy. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT3	NM_057088.3	c.1536-69C>T		intron_variant		ENST00000417996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT3	ENST00000417996.2	c.1536-69C>T		intron_variant		1	NM_057088.3	P1

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11976 AN: 152110 Hom.: 1290 Cov.: 33

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0745

GnomAD4 exome AF: 0.0583 AC: 75592 AN: 1297014 Hom.: 7307 AF XY: 0.0592 AC XY: 38296 AN XY: 646730

Gnomad4 AFR exome AF: 0.0718

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.0233

Gnomad4 EAS exome AF: 0.470

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0553

Gnomad4 NFE exome AF: 0.0306

Gnomad4 OTH exome AF: 0.0792

GnomAD4 genome AF: 0.0789 AC: 12004 AN: 152228 Hom.: 1304 Cov.: 33 AF XY: 0.0851 AC XY: 6337 AN XY: 74428

Gnomad4 AFR AF: 0.0711

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0655

Gnomad4 NFE AF: 0.0295

Gnomad4 OTH AF: 0.0742

Alfa AF: 0.0460 Hom.: 89

Bravo AF: 0.0929

Asia WGS AF: 0.297 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.59

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: rs12312467; hg19: chr12-53184725;