Genetic Variant KRTAP19-3:p.Gly60Arg (chr21-30491780-C-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_181609.4(KRTAP19-3):c.178G>C(p.Gly60Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G60A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP19-3
NM_181609.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0820

Publications

5 publications found

Variant links:

Genes affected

KRTAP19-3 (HGNC:18938): (keratin associated protein 19-3) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP19-3 links:

ENSG00000303806 (HGNC:):

ENSG00000303806 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=0.10854092).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181609.4. 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
	KRTAP19-3	NM_181609.4	MANE Select	c.178G>C	p.Gly60Arg	missense	Exon 1 of 1	NP_853640.1	Q7Z4W3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP19-3	ENST00000334063.6	TSL:6 MANE Select	c.178G>C	p.Gly60Arg	missense	Exon 1 of 1	ENSP00000386376.2	Q7Z4W3
ENSG00000303806	ENST00000797282.1		n.118-7190C>G		intron	N/A
ENSG00000303806	ENST00000797283.1		n.118-9216C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251488

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111984

Other (OTH)

AF:

0.00

AC:

AN:

60396

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

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.8

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.12

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.34

M_CAP

Benign

0.0031

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

PhyloP100

0.082

PROVEAN

Benign

0.67

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.012

Polyphen

0.59

Vest4

0.26

MutPred

0.22

Gain of methylation at G60 (P = 0.0079)

MVP

0.21

MPC

0.043

ClinPred

0.49

GERP RS

-0.36

PromoterAI

-0.0068

Neutral

(source)

Varity_R

0.14

gMVP

0.056

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

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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