Genetic Variant NM_001004325.2:c.82T>C (chr11-1598169-A-G) – 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_001004325.2(KRTAP5-2):c.82T>C(p.Cys28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,388,900 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: 𝑓 0.0000083 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP5-2
NM_001004325.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.600

Publications

0 publications found

Variant links:

Genes affected

KRTAP5-2 (HGNC:23597): (keratin associated protein 5-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-2 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=0.18802956).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004325.2. 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
	KRTAP5-2	NM_001004325.2	MANE Select	c.82T>C	p.Cys28Arg	missense	Exon 1 of 1	NP_001004325.1	Q701N4
	KRTAP5-AS1	NR_021489.2		n.1250A>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP5-2	ENST00000412090.2	TSL:6 MANE Select	c.82T>C	p.Cys28Arg	missense	Exon 1 of 1	ENSP00000400041.1	Q701N4
KRTAP5-AS1	ENST00000424148.1	TSL:2	n.1250A>G		non_coding_transcript_exon	Exon 2 of 2
KRTAP5-AS1	ENST00000792906.1		n.214-14196A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000831

AC:

AN:

120384

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000333

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000288

AC:

AN:

1388900

Hom.:

Cov.:

AF XY:

0.00000579

AC XY:

AN XY:

691186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31434

American (AMR)

AF:

0.00

AC:

AN:

42798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24128

East Asian (EAS)

AF:

0.00

AC:

AN:

33780

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4306

European-Non Finnish (NFE)

AF:

0.00000282

AC:

AN:

1064144

Other (OTH)

AF:

0.00

AC:

AN:

56086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000831

AC:

AN:

120384

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

57028

show subpopulations

African (AFR)

AF:

0.0000333

AC:

AN:

30020

American (AMR)

AF:

0.00

AC:

AN:

9900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3120

East Asian (EAS)

AF:

0.00

AC:

AN:

3960

South Asian (SAS)

AF:

0.00

AC:

AN:

3526

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60396

Other (OTH)

AF:

0.00

AC:

AN:

1604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

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

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.20

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.31

M_CAP

Benign

0.0032

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.2

PhyloP100

0.60

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.086

Sift4G

Pathogenic

0.0

Polyphen

0.91

Vest4

0.36

MutPred

0.37

Gain of methylation at C28 (P = 0.0229)

MVP

0.18

MPC

0.16

ClinPred

0.42

GERP RS

1.9

PromoterAI

-0.0040

Neutral

(source)

Varity_R

0.67

gMVP

0.11

Mutation Taster

=100/0

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