chr12-52592403-T-C

Position:

• chr12-52592403-T-C

Variant summary

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

The NM_080747.3(KRT72):​c.791A>G​(p.Tyr264Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,606,810 control chromosomes in the GnomAD database, including 122,080 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.35 (9806 hom., cov: 33)
  • Exomes 𝑓: 0.39 (112274 hom.)
• Consequence: KRT72 NM_080747.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372

Genes affected

KRT72 (HGNC:28932): (keratin 72) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells. The type II keratins 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 gene encodes a type II keratin that is specifically expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q12-q13. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.8046966E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT72	NM_080747.3	c.791A>G	p.Tyr264Cys	missense_variant	4/9	ENST00000293745.7	NP_542785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT72	ENST00000293745.7	c.791A>G	p.Tyr264Cys	missense_variant	4/9	1	NM_080747.3	ENSP00000293745.2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52630 AN: 152012 Hom.: 9785 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.357

GnomAD3 exomes AF: 0.383 AC: 96191 AN: 251048 Hom.: 19917 AF XY: 0.396 AC XY: 53701 AN XY: 135676

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.608

Gnomad SAS exome AF: 0.497

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.383

Gnomad OTH exome AF: 0.377

GnomAD4 exome AF: 0.387 AC: 562782 AN: 1454680 Hom.: 112274 Cov.: 30 AF XY: 0.392 AC XY: 283622 AN XY: 724180

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.561

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.385

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.346 AC: 52696 AN: 152130 Hom.: 9806 Cov.: 33 AF XY: 0.349 AC XY: 25956 AN XY: 74354

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.361

Alfa AF: 0.383 Hom.: 28311

Bravo AF: 0.328

TwinsUK AF: 0.381 AC: 1413

ALSPAC AF: 0.385 AC: 1484

ESP6500AA AF: 0.258 AC: 1138

ESP6500EA AF: 0.382 AC: 3281

ExAC AF: 0.387 AC: 46958

Asia WGS AF: 0.506 AC: 1757 AN: 3478

EpiCase AF: 0.389

EpiControl AF: 0.389

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;D;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.68	.;T;T
MetaRNN	Benign	0.00028	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.5	M;M;M
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-7.3	D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.013	B;B;.
Vest4		0.68
MPC		0.32
ClinPred		0.11	T
GERP RS		3.7
Varity_R		0.44
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs12833456; hg19: chr12-52986187; COSMIC: COSV53373203;