Genetic Variant NM_001005922.1:c.263G>A (chr11-1584987-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005922.1(KRTAP5-1):c.263G>A(p.Gly88Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,278,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 14)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

KRTAP5-1
NM_001005922.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.136

Publications

1 publications found

Variant links:

Genes affected

KRTAP5-1 (HGNC:23596): (keratin associated protein 5-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-1 links:

KRTAP5-AS1 (HGNC:27877): (KRTAP5-1/KRTAP5-2 antisense RNA 1)

KRTAP5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16228735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005922.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-1	NM_001005922.1	MANE Select	c.263G>A	p.Gly88Asp	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11919C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP5-1	ENST00000382171.2	TSL:6 MANE Select	c.263G>A	p.Gly88Asp	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11919C>T		intron	N/A
KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12261C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000122

AC:

AN:

245870

AF XY:

0.00000751

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000266

AC:

AN:

1278780

Hom.:

Cov.:

AF XY:

0.0000252

AC XY:

AN XY:

634880

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28136

American (AMR)

AF:

0.00

AC:

AN:

37640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19588

East Asian (EAS)

AF:

0.00

AC:

AN:

26068

South Asian (SAS)

AF:

0.00

AC:

AN:

78216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3264

European-Non Finnish (NFE)

AF:

0.0000322

AC:

AN:

994470

Other (OTH)

AF:

0.0000410

AC:

AN:

48836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000337

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.10

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.22

M_CAP

Benign

0.0040

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

PhyloP100

-0.14

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.054

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.038

Polyphen

0.40

Vest4

0.48

MutPred

0.24

Gain of ubiquitination at K86 (P = 0.0381)

MVP

0.20

MPC

0.049

ClinPred

0.13

GERP RS

2.8

PromoterAI

0.00080

Neutral

(source)

Varity_R

0.15

gMVP

0.060

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over