12-52618518-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_175068.3(KRT73):c.7C>A(p.Arg3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,445,330 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT73	NM_175068.3	c.7C>A	p.Arg3Ser	missense_variant	1/9	ENST00000305748.7
KRT73	XM_047428761.1	c.7C>A	p.Arg3Ser	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT73	ENST00000305748.7	c.7C>A	p.Arg3Ser	missense_variant	1/9	1	NM_175068.3	P1
KRT73	ENST00000546934.1	n.32C>A		non_coding_transcript_exon_variant	1/8	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000422 AC: 1 AN: 237038 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 128370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000939

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1445330 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717128

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.06e-7

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.59	D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.024	D
Polyphen		0.96	P
Vest4		0.59
MutPred		0.50		Loss of MoRF binding (P = 0.0054);
MVP		0.49
MPC		0.62
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.63
gMVP		0.44

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;