Genetic Variant NM_175078.3:c.1499C>A (chr12-52691403-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175078.3(KRT77):c.1499C>A(p.Ala500Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A500V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRT77
NM_175078.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.278

Publications

0 publications found

Variant links:

Genes affected

KRT77 (HGNC:20411): (keratin 77) 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 an epithelial keratin that is expressed in the skin and eccrine sweat glands. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

KRT77 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0870364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175078.3. 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
	KRT77	NM_175078.3	MANE Select	c.1499C>A	p.Ala500Glu	missense	Exon 9 of 9	NP_778253.2	Q7Z794

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT77	ENST00000341809.8	TSL:1 MANE Select	c.1499C>A	p.Ala500Glu	missense	Exon 9 of 9	ENSP00000342710.3	Q7Z794
KRT77	ENST00000553168.1	TSL:1	n.*837C>A		non_coding_transcript_exon	Exon 10 of 10	ENSP00000448207.1	F8VS61
KRT77	ENST00000553168.1	TSL:1	n.*837C>A		3_prime_UTR	Exon 10 of 10	ENSP00000448207.1	F8VS61

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1446750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719402

African (AFR)

AF:

0.00

AC:

AN:

33268

American (AMR)

AF:

0.00

AC:

AN:

44136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25668

East Asian (EAS)

AF:

0.00

AC:

AN:

39548

South Asian (SAS)

AF:

0.00

AC:

AN:

85256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45018

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5408

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108540

Other (OTH)

AF:

0.00

AC:

AN:

59908

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Benign

9.0

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0028

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.11

M_CAP

Benign

0.013

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.0

PhyloP100

-0.28

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.1

REVEL

Benign

0.20

Sift

Benign

0.23

Sift4G

Benign

0.20

Polyphen

0.41

Vest4

0.093

MutPred

0.31

Gain of solvent accessibility (P = 0.005)

MVP

0.48

MPC

0.22

ClinPred

0.18

GERP RS

-1.1

Varity_R

0.061

gMVP

0.58

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over