Genetic Variant KRT73:p.Val367Met (chr12-52611215-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_175068.3(KRT73):c.1099G>A(p.Val367Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KRT73
NM_175068.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.504

Variant links:

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 links:

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

KRT73-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3020563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT73	NM_175068.3 link	c.1099G>A	p.Val367Met	missense_variant	Exon 6 of 9	ENST00000305748.7	NP_778238.1	Q86Y46-1
KRT73	XM_047428761.1 link	c.1099G>A	p.Val367Met	missense_variant	Exon 8 of 11		XP_047284717.1
KRT73-AS1	NR_126005.1 link	n.1365C>T		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT73	ENST00000305748.7 link	c.1099G>A	p.Val367Met	missense_variant	Exon 6 of 9	1	NM_175068.3	ENSP00000307014.3		Q86Y46-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1099G>A (p.V367M) alteration is located in exon 6 (coding exon 6) of the KRT73 gene. This alteration results from a G to A substitution at nucleotide position 1099, causing the valine (V) at amino acid position 367 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;.

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.30

T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.4

N;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

0.74

P;.

Vest4

0.24

MutPred

0.55

Gain of ubiquitination at K369 (P = 0.0645);.;

MVP

0.38

MPC

0.28

ClinPred

0.92

GERP RS

5.6

Varity_R

0.28

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over