Genetic Variant KRT222:p.Ala85Val (chr17-40660179-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152349.3(KRT222):c.254C>T(p.Ala85Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000253 in 1,461,802 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: 31)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

KRT222
NM_152349.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

Publications

0 publications found

Variant links:

Genes affected

KRT222 (HGNC:28695): (keratin 222) Predicted to enable structural molecule activity. Predicted to be located in intermediate filament. [provided by Alliance of Genome Resources, Apr 2022]

KRT222 links:

ENSG00000264058 (HGNC:):

ENSG00000264058 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3813171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT222	NM_152349.3 link	c.254C>T	p.Ala85Val	missense_variant	Exon 3 of 6	ENST00000394052.5	NP_689562.1	Q8N1A0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT222	ENST00000394052.5 link	c.254C>T	p.Ala85Val	missense_variant	Exon 3 of 6	1	NM_152349.3	ENSP00000377616.3		Q8N1A0-1
ENSG00000264058	ENST00000476049.1 link	n.254C>T		non_coding_transcript_exon_variant	Exon 3 of 13	5		ENSP00000463483.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251322

AF XY:

0.00000736

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1111980

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.254C>T (p.A85V) alteration is located in exon 3 (coding exon 3) of the KRT222 gene. This alteration results from a C to T substitution at nucleotide position 254, causing the alanine (A) at amino acid position 85 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.056

MetaRNN

Benign

0.38

MetaSVM

Uncertain

0.28

MutationAssessor

Benign

1.2

PhyloP100

4.1

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.49

Sift

Uncertain

0.0090

Sift4G

Benign

0.23

Polyphen

0.38

Vest4

0.50

MutPred

0.48

Loss of disorder (P = 0.1987);

MVP

0.74

MPC

0.42

ClinPred

0.90

GERP RS

4.7

Varity_R

0.13

gMVP

0.30

Mutation Taster

=75/25

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

17-40660179-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over