rs35725856

Variant summary

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

The NM_182507.3(KRT80):​c.712G>T​(p.Val238Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,459,994 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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. V238I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

KRT80
NM_182507.3 missense

Scores

8
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.841
Variant links:
Genes affected
KRT80 (HGNC:27056): (keratin 80) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene's expression profile shows that it encodes a type II epithelial keratin, although structurally the encoded protein is more like a type II hair keratin. This protein is involved in cell differentiation, localizing near desmosomal plaques in earlier stages of differentiation but then dispersing throughout the cytoplasm in terminally differentiating cells. The type II keratins are clustered in a region of chromosome 12q13. Two transcript variants encoding two different fully functional isoforms have been found for this gene.[provided by RefSeq, Oct 2010]
LINC00592 (HGNC:27474): (long intergenic non-protein coding RNA 592)

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ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
KRT80NM_182507.3 linkc.712G>T p.Val238Phe missense_variant Exon 5 of 9 ENST00000394815.3 NP_872313.2 Q6KB66-1
KRT80NM_001081492.2 linkc.712G>T p.Val238Phe missense_variant Exon 5 of 9 NP_001074961.1 Q6KB66-2
KRT80XM_005268676.4 linkc.817G>T p.Val273Phe missense_variant Exon 3 of 7 XP_005268733.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRT80ENST00000394815.3 linkc.712G>T p.Val238Phe missense_variant Exon 5 of 9 1 NM_182507.3 ENSP00000378292.2 Q6KB66-1
KRT80ENST00000313234.9 linkc.712G>T p.Val238Phe missense_variant Exon 5 of 9 1 ENSP00000369361.2 Q6KB66-2
KRT80ENST00000466011.1 linkn.868G>T non_coding_transcript_exon_variant Exon 3 of 7 2
LINC00592ENST00000640420.1 linkn.413+8768C>A intron_variant Intron 2 of 2 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249318
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135096
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 SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1459994
Hom.:
0
Cov.:
32
AF XY:
0.0000165
AC XY:
12
AN XY:
726440
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.0000194
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.070
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
11
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.61
.;D
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.073
D
MetaRNN
Uncertain
0.49
T;T
MetaSVM
Uncertain
0.35
D
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-2.2
N;N
REVEL
Uncertain
0.48
Sift
Uncertain
0.016
D;D
Sift4G
Uncertain
0.020
D;D
Polyphen
0.94
P;P
Vest4
0.41
MutPred
0.58
Gain of catalytic residue at R243 (P = 0);Gain of catalytic residue at R243 (P = 0);
MVP
0.55
MPC
0.15
ClinPred
0.31
T
GERP RS
0.032
Varity_R
0.27
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs35725856; hg19: chr12-52567503; API