rs777526892

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002280.6(KRT35):​c.1355G>T​(p.Gly452Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G452E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

KRT35
NM_002280.6 missense

Scores

9
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.65
Variant links:
Genes affected
KRT35 (HGNC:6453): (keratin 35) The protein encoded by this gene is a member of the keratin gene family. This type I hair keratin is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24412242).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRT35NM_002280.6 linkc.1355G>T p.Gly452Val missense_variant Exon 7 of 7 ENST00000246639.7 NP_002271.3 Q92764

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRT35ENST00000246639.7 linkc.1355G>T p.Gly452Val missense_variant Exon 7 of 7 1 NM_002280.6 ENSP00000246639.3 Q92764C4AM86

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
7.02e-7
AC:
1
AN:
1425234
Hom.:
0
Cov.:
48
AF XY:
0.00000141
AC XY:
1
AN XY:
707386
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:
9.11e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0081
T;T
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.24
T;T
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Uncertain
2.1
.;M
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.040
N;N
REVEL
Uncertain
0.43
Sift
Uncertain
0.016
D;D
Sift4G
Benign
0.073
T;T
Polyphen
0.54
.;P
Vest4
0.40
MutPred
0.29
.;Loss of methylation at R454 (P = 0.046);
MVP
0.61
MPC
0.18
ClinPred
0.92
D
GERP RS
5.4
Varity_R
0.17
gMVP
0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-39633321; API