rs1567759

chr12-52697782-C-Achr12-52697782-C-T

Variant summary

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

The NM_175078.3(KRT77):c.658G>T(p.Gly220Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,613,712 control chromosomes in the GnomAD database, including 143,479 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.43 (14125 hom., cov: 31)
  • Exomes 𝑓: 0.42 (129354 hom.)
• Consequence: KRT77 NM_175078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

Genes affected

KRT77 (HGNC:20411): (keratin 77) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes an epithelial keratin that is expressed in the skin and eccrine sweat glands. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3282895E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT77	NM_175078.3	c.658G>T	p.Gly220Cys	missense_variant	2/9	ENST00000341809.8
KRT77	XM_011538289.3	c.658G>T	p.Gly220Cys	missense_variant	2/5
KRT77	XM_011538288.3	c.-42G>T		5_prime_UTR_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT77	ENST00000341809.8	c.658G>T	p.Gly220Cys	missense_variant	2/9	1	NM_175078.3	P1
KRT77	ENST00000553168.1	c.743G>T	p.Arg248Leu	missense_variant, NMD_transcript_variant	3/10	1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64854 AN: 151858 Hom.: 14091 Cov.: 31

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.402

GnomAD3 exomes AF: 0.404 AC: 101643 AN: 251488 Hom.: 20969 AF XY: 0.406 AC XY: 55168 AN XY: 135916

Gnomad AFR exome AF: 0.451

Gnomad AMR exome AF: 0.353

Gnomad ASJ exome AF: 0.426

Gnomad EAS exome AF: 0.249

Gnomad SAS exome AF: 0.424

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.425

Gnomad OTH exome AF: 0.386

GnomAD4 exome AF: 0.418 AC: 611501 AN: 1461736 Hom.: 129354 Cov.: 44 AF XY: 0.418 AC XY: 304297 AN XY: 727184

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.444

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.412

GnomAD4 genome AF: 0.427 AC: 64930 AN: 151976 Hom.: 14125 Cov.: 31 AF XY: 0.425 AC XY: 31536 AN XY: 74284

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.408

Alfa AF: 0.419 Hom.: 23987

Bravo AF: 0.423

TwinsUK AF: 0.445 AC: 1650

ALSPAC AF: 0.439 AC: 1690

ESP6500AA AF: 0.451 AC: 1988

ESP6500EA AF: 0.422 AC: 3625

ExAC AF: 0.408 AC: 49523

Asia WGS AF: 0.420 AC: 1462 AN: 3478

EpiCase AF: 0.417

EpiControl AF: 0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	15
Dann	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.00013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.29
Sift	Benign	0.033	D
Sift4G	Uncertain	0.055	T
Polyphen		1.0	D
Vest4		0.067
MPC		0.74
ClinPred		0.032	T
GERP RS		-2.0
Varity_R		0.14
gMVP		0.11

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: rs1567759; hg19: chr12-53091566; COSMIC: COSV59238867; COSMIC: COSV59238867;