Genetic Variant KRTAP9-1:p.Ala73Thr (chr17-41190103-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001190460.1(KRTAP9-1):c.217G>A(p.Ala73Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000494 in 1,599,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

KRTAP9-1
NM_001190460.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.54

Variant links:

Genes affected

KRTAP9-1 (HGNC:18912): (keratin associated protein 9-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP9-1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016030788).

BP6

Variant 17-41190103-G-A is Benign according to our data. Variant chr17-41190103-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3536614.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP9-1	NM_001190460.1 link	c.217G>A	p.Ala73Thr	missense_variant	Exon 1 of 1	ENST00000398470.1	NP_001177389.1	A8MXZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP9-1	ENST00000398470.1 link	c.217G>A	p.Ala73Thr	missense_variant	Exon 1 of 1	6	NM_001190460.1	ENSP00000381488.1		A8MXZ3

Frequencies

GnomAD3 genomes

AF:

0.000240

AC:

AN:

149776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000838

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.000492

GnomAD3 exomes

AF:

0.0000600

AC:

AN:

250174

Hom.:

AF XY:

0.0000665

AC XY:

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.000941

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000297

AC:

AN:

1449150

Hom.:

Cov.:

115

AF XY:

0.0000305

AC XY:

AN XY:

720406

show subpopulations

Gnomad4 AFR exome

AF:

0.000823

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000357

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000994

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.000240

AC:

AN:

149892

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

AN XY:

73158

show subpopulations

Gnomad4 AFR

AF:

0.000835

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.000486

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000227

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 09, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0020

DANN

Benign

0.40

DEOGEN2

Benign

0.00088

T;.;.;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.0083

T;T;T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.016

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.9

N;.;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

2.3

N;.;.;.

REVEL

Benign

0.029

Sift

Benign

0.87

T;.;.;.

Sift4G

Benign

0.70

T;T;T;T

Vest4

0.023

MVP

0.030

MPC

0.028

ClinPred

0.035

GERP RS

-5.6

Varity_R

0.017

gMVP

0.040

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.

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