chr12-52592403-T-C

Variant names:

• chr12-52592403-T-C
• rs12833456
• NM_080747.3:c.791A>G

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KRT72	NM_080747.3	c.791A>G	p.Tyr264Cys	missense_variant	Exon 4 of 9	ENST00000293745.7	NP_542785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT72	ENST00000293745.7	c.791A>G	p.Tyr264Cys	missense_variant	Exon 4 of 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

GnomAD2 exomes AF: 0.383 AC: 96191 AN: 251048 AF XY: 0.396

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 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

African (AFR) AF: 0.240 AC: 8008 AN: 33358

American (AMR) AF: 0.223 AC: 9958 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 10856 AN: 26070

East Asian (EAS) AF: 0.561 AC: 22257 AN: 39654

South Asian (SAS) AF: 0.498 AC: 42809 AN: 86046

European-Finnish (FIN) AF: 0.385 AC: 20557 AN: 53398

Middle Eastern (MID) AF: 0.349 AC: 2008 AN: 5752

European-Non Finnish (NFE) AF: 0.382 AC: 422868 AN: 1105612

Other (OTH) AF: 0.390 AC: 23461 AN: 60140

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

African (AFR) AF: 0.241 AC: 10012 AN: 41510

American (AMR) AF: 0.256 AC: 3914 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1468 AN: 3468

East Asian (EAS) AF: 0.588 AC: 3040 AN: 5170

South Asian (SAS) AF: 0.515 AC: 2482 AN: 4820

European-Finnish (FIN) AF: 0.391 AC: 4141 AN: 10586

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26219 AN: 67984

Other (OTH) AF: 0.361 AC: 760 AN: 2108

Alfa AF: 0.377 Hom.: 50004

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
PhyloP100		0.37
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12833456; hg19: chr12-52986187; COSMIC: COSV53373203;