rs76875855

chr12-52618518-G-Achr12-52618518-G-Cchr12-52618518-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_175068.3(KRT73):c.7C>T(p.Arg3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000956 in 1,597,616 control chromosomes in the GnomAD database, including 55 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 0.00055 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (49 hom.)
• Consequence: KRT73 NM_175068.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

Genes affected

KRT73 (HGNC:28928): (keratin 73) 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 a protein that is expressed in the inner root sheath of hair follicles. 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=0.016466051).
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.001 (1445/1445330) while in subpopulation EAS AF= 0.034 (1342/39456). AF 95% confidence interval is 0.0325. There are 49 homozygotes in gnomad4_exome. There are 701 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT73	NM_175068.3	c.7C>T	p.Arg3Cys	missense_variant	1/9	ENST00000305748.7
KRT73	XM_047428761.1	c.7C>T	p.Arg3Cys	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT73	ENST00000305748.7	c.7C>T	p.Arg3Cys	missense_variant	1/9	1	NM_175068.3	P1
KRT73	ENST00000546934.1	n.32C>T		non_coding_transcript_exon_variant	1/8	2

Frequencies

GnomAD3 genomes AF: 0.000545 AC: 83 AN: 152168 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000232 AC: 55 AN: 237038 Hom.: 0 AF XY: 0.000203 AC XY: 26 AN XY: 128370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000914

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00176

Gnomad SAS exome AF: 0.000283

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000939

Gnomad OTH exome AF: 0.000348

GnomAD4 exome AF: 0.00100 AC: 1445 AN: 1445330 Hom.: 49 Cov.: 32 AF XY: 0.000978 AC XY: 701 AN XY: 717128

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000932

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0340

Gnomad4 SAS exome AF: 0.000261

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000489

Gnomad4 OTH exome AF: 0.000370

GnomAD4 genome AF: 0.000545 AC: 83 AN: 152286 Hom.: 6 Cov.: 33 AF XY: 0.000631 AC XY: 47 AN XY: 74466

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000121 Hom.: 0

Bravo AF: 0.000230

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000288 AC: 35

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.12
Cadd	Pathogenic	27
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.86	D
MetaRNN	Benign	0.016	T
MetaSVM	Uncertain	0.25	D
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.037	D
Polyphen		1.0	D
Vest4		0.67
MVP		0.51
MPC		0.69
ClinPred		0.17	T
GERP RS		4.5
Varity_R		0.25
gMVP		0.39

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: rs76875855; hg19: chr12-53012302; COSMIC: COSV105898705; COSMIC: COSV105898705;