Variant 21-30480124-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_181607.3(KRTAP19-1):c.194G>A(p.Gly65Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000331 in 1,600,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

KRTAP19-1
NM_181607.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

Variant links:

Genes affected

KRTAP19-1 (HGNC:18936): (keratin associated protein 19-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP19-1 links:

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=0.23618808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP19-1	NM_181607.3 linkuse as main transcript	c.194G>A	p.Gly65Asp	missense_variant	1/1	ENST00000390689.3	NP_853638.1	Q8IUB9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP19-1	ENST00000390689.3 linkuse as main transcript	c.194G>A	p.Gly65Asp	missense_variant	1/1	6	NM_181607.3	ENSP00000375108.2		Q8IUB9

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151434

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251478

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135912

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000359

AC:

AN:

1448818

Hom.:

Cov.:

AF XY:

0.0000402

AC XY:

AN XY:

720754

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:

0.0000464

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74014

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

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

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Oct 03, 2024

The c.194G>A (p.G65D) alteration is located in exon 1 (coding exon 1) of the KRTAP19-1 gene. This alteration results from a G to A substitution at nucleotide position 194, causing the glycine (G) at amino acid position 65 to be replaced by an aspartic acid (D). 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.8

DANN

Benign

0.43

DEOGEN2

Benign

0.16

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.64

M_CAP

Benign

0.027

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.0

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.096

Sift4G

Uncertain

0.0050

Polyphen

0.30

Vest4

0.59

MutPred

0.19

Loss of sheet (P = 0.0817);

MVP

0.26

MPC

0.15

ClinPred

0.098

GERP RS

2.0

Varity_R

0.38

gMVP

0.26

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.

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