NM_001099219.1:c.131A>G

Variant summary

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

The NM_001099219.1(KRTAP19-8):​c.131A>G​(p.Tyr44Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y44H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KRTAP19-8
NM_001099219.1 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.660
Variant links:
Genes affected
KRTAP19-8 (HGNC:33898): (keratin associated protein 19-8) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.18414935).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP19-8NM_001099219.1 linkc.131A>G p.Tyr44Cys missense_variant Exon 1 of 1 ENST00000382822.2 NP_001092689.1 Q3LI54

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP19-8ENST00000382822.2 linkc.131A>G p.Tyr44Cys missense_variant Exon 1 of 1 6 NM_001099219.1 ENSP00000372272.2 Q3LI54

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251034
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135756
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459994
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726478
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.131A>G (p.Y44C) alteration is located in exon 1 (coding exon 1) of the KRTAP19-8 gene. This alteration results from a A to G substitution at nucleotide position 131, causing the tyrosine (Y) at amino acid position 44 to be replaced by a cysteine (C). 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
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
6.5
DANN
Benign
0.77
DEOGEN2
Benign
0.091
T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.046
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-3.8
D
REVEL
Benign
0.029
Sift
Benign
0.14
T
Sift4G
Uncertain
0.016
D
Polyphen
1.0
D
Vest4
0.21
MutPred
0.21
Gain of sheet (P = 0.0827);
MVP
0.12
MPC
0.20
ClinPred
0.31
T
GERP RS
2.8
Varity_R
0.13
gMVP
0.059

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.

Other links and lift over

dbSNP: rs763630791; hg19: chr21-32410632; API