Variant 12-52361013-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002283.4(KRT85):c.1364G>C(p.Gly455Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,344 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

KRT85
NM_002283.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

Variant links:

Genes affected

KRT85 (HGNC:6462): (keratin 85) The protein encoded by this gene is a member of the keratin gene family. As a type II hair keratin, it is a basic protein which heterodimerizes with type I keratins to form hair and nails. The type II hair keratins are clustered in a region of chromosome 12q13 and are grouped into two distinct subfamilies based on structure similarity. One subfamily, consisting of KRTHB1, KRTHB3, and KRTHB6, is highly related. The other less-related subfamily includes KRTHB2, KRTHB4, and KRTHB5. [provided by RefSeq, Jul 2008]

KRT85 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=0.3636135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT85	NM_002283.4 linkuse as main transcript	c.1364G>C	p.Gly455Ala	missense_variant	9/9	ENST00000257901.7	NP_002274.1	P78386
KRT85	NM_001300810.1 linkuse as main transcript	c.728G>C	p.Gly243Ala	missense_variant	7/7		NP_001287739.1	P78386F5GYI5B7Z7N3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT85	ENST00000257901.7 linkuse as main transcript	c.1364G>C	p.Gly455Ala	missense_variant	9/9	1	NM_002283.4	ENSP00000257901.3		P78386
KRT85	ENST00000544265.1 linkuse as main transcript	c.728G>C	p.Gly243Ala	missense_variant	7/7	2		ENSP00000440240.1		F5GYI5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461196

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726890

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:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.1364G>C (p.G455A) alteration is located in exon 9 (coding exon 9) of the KRT85 gene. This alteration results from a G to C substitution at nucleotide position 1364, causing the glycine (G) at amino acid position 455 to be replaced by an alanine (A). 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

0.048

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.094

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.055

MetaRNN

Benign

0.36

T;T

MetaSVM

Uncertain

-0.046

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.028

D;D

Sift4G

Uncertain

0.031

D;D

Polyphen

1.0

D;.

Vest4

0.36

MutPred

0.32

Gain of catalytic residue at S458 (P = 5e-04);.;

MVP

0.90

MPC

0.41

ClinPred

0.95

GERP RS

5.0

Varity_R

0.32

gMVP

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over