12-52608297-G-A

Variant names:

• chr12-52608297-G-A
• rs116777147
• NM_175068.3:c.1522C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_175068.3(KRT73):​c.1522C>T​(p.Arg508Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000894 in 1,613,822 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00094 (2 hom.)
• Consequence: KRT73 NM_175068.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.415
• Publications: 2 publications found

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]

KRT73-AS1 (HGNC:49607): (KRT73 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03374222).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175068.3. 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
	KRT73	NM_175068.3	MANE Select	c.1522C>T	p.Arg508Cys	missense	Exon 9 of 9	NP_778238.1	Q86Y46-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT73	ENST00000305748.7	TSL:1 MANE Select	c.1522C>T	p.Arg508Cys	missense	Exon 9 of 9	ENSP00000307014.3	Q86Y46-1
	KRT73	ENST00000552855.1	TSL:3	c.757C>T	p.Arg253Cys	missense	Exon 6 of 6	ENSP00000449081.1	H0YIC5
	KRT73	ENST00000546934.1	TSL:2	n.1915C>T		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.000454 AC: 69 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000502 AC: 126 AN: 250810 AF XY: 0.000443

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000970

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000941 AC: 1376 AN: 1461596 Hom.: 2 Cov.: 31 AF XY: 0.000916 AC XY: 666 AN XY: 727078

African (AFR) AF: 0.0000597 AC: 2 AN: 33476

American (AMR) AF: 0.000112 AC: 5 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86170

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00118 AC: 1317 AN: 1111934

Other (OTH) AF: 0.000563 AC: 34 AN: 60378

GnomAD4 genome AF: 0.000440 AC: 67 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74416

African (AFR) AF: 0.000193 AC: 8 AN: 41540

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000809 AC: 55 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000787 Hom.: 2

Bravo AF: 0.000450

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.000642 AC: 78

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.00130

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.41
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.46
Sift	Benign	0.030	D
Sift4G	Benign	0.18	T
Polyphen		0.028	B
Vest4		0.23
MVP		0.41
MPC		0.18
ClinPred		0.019	T
GERP RS		3.2
Varity_R		0.076
gMVP		0.27
Mutation Taster		=88/12	polymorphism

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: rs116777147; hg19: chr12-53002081;