12-52697782-C-A

Variant names:

• chr12-52697782-C-A
• rs1567759
• NM_175078.3:c.658G>T

Variant summary

Our verdict is Benign. The variant received -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. 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: 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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT77	NM_175078.3	MANE Select	c.658G>T	p.Gly220Cys	missense	Exon 2 of 9	NP_778253.2	Q7Z794

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT77	ENST00000341809.8	TSL:1 MANE Select	c.658G>T	p.Gly220Cys	missense	Exon 2 of 9	ENSP00000342710.3	Q7Z794
	KRT77	ENST00000553168.1	TSL:1	n.743G>T		non_coding_transcript_exon	Exon 3 of 10	ENSP00000448207.1	F8VS61

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

GnomAD2 exomes AF: 0.404 AC: 101643 AN: 251488 AF XY: 0.406

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 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

African (AFR) AF: 0.454 AC: 15184 AN: 33480

American (AMR) AF: 0.359 AC: 16075 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 11275 AN: 26130

East Asian (EAS) AF: 0.228 AC: 9049 AN: 39692

South Asian (SAS) AF: 0.426 AC: 36712 AN: 86258

European-Finnish (FIN) AF: 0.444 AC: 23689 AN: 53412

Middle Eastern (MID) AF: 0.353 AC: 2036 AN: 5766

European-Non Finnish (NFE) AF: 0.425 AC: 472599 AN: 1111894

Other (OTH) AF: 0.412 AC: 24882 AN: 60386

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

African (AFR) AF: 0.453 AC: 18787 AN: 41452

American (AMR) AF: 0.392 AC: 5991 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1497 AN: 3472

East Asian (EAS) AF: 0.245 AC: 1267 AN: 5164

South Asian (SAS) AF: 0.452 AC: 2174 AN: 4810

European-Finnish (FIN) AF: 0.446 AC: 4700 AN: 10532

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28949 AN: 67950

Other (OTH) AF: 0.408 AC: 863 AN: 2114

Alfa AF: 0.422 Hom.: 50239

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 v4.9

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
PhyloP100		-1.9
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
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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