Genetic Variant KRTAP5-1:p.Gly114Gly (chr11-1584908-T-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_001005922.1(KRTAP5-1):c.342A>C(p.Gly114Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.029 ( 1 hom., cov: 0)

Exomes 𝑓: 0.011 ( 95 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP5-1
NM_001005922.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Publications

3 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP7

Synonymous conserved (PhyloP=-2.04 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-1	NM_001005922.1 link	c.342A>C	p.Gly114Gly	synonymous_variant	Exon 1 of 1	ENST00000382171.2	NP_001005922.1	Q6L8H4
KRTAP5-AS1	NR_021489.2 link	n.328+11840T>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-1	ENST00000382171.2 link	c.342A>C	p.Gly114Gly	synonymous_variant	Exon 1 of 1	6	NM_001005922.1	ENSP00000371606.2		Q6L8H4

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

138

AN:

4630

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0246

Gnomad AMI

AF:

0.0313

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.0250

Gnomad EAS

AF:

0.0238

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.0407

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0348

Gnomad OTH

AF:

0.0500

GnomAD2 exomes

AF:

0.0104

AC:

2089

AN:

200984

AF XY:

0.0105

show subpopulations

Gnomad AFR exome

AF:

0.00459

Gnomad AMR exome

AF:

0.00980

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.00438

Gnomad FIN exome

AF:

0.00744

Gnomad NFE exome

AF:

0.0111

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0108

AC:

2695

AN:

249910

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

1326

AN XY:

122298

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0129

AC:

AN:

5030

American (AMR)

AF:

0.0139

AC:

124

AN:

8924

Ashkenazi Jewish (ASJ)

AF:

0.0116

AC:

AN:

5426

East Asian (EAS)

AF:

0.00534

AC:

AN:

6176

South Asian (SAS)

AF:

0.0109

AC:

155

AN:

14260

European-Finnish (FIN)

AF:

0.0296

AC:

152

AN:

5136

Middle Eastern (MID)

AF:

0.00911

AC:

AN:

768

European-Non Finnish (NFE)

AF:

0.0102

AC:

1979

AN:

193952

Other (OTH)

AF:

0.0114

AC:

117

AN:

10238

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.277

Heterozygous variant carriers

223

446

670

893

1116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.0294

AC:

137

AN:

4654

Hom.:

Cov.:

AF XY:

0.0285

AC XY:

AN XY:

2246

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0242

AC:

AN:

950

American (AMR)

AF:

0.0109

AC:

AN:

366

Ashkenazi Jewish (ASJ)

AF:

0.0250

AC:

AN:

160

East Asian (EAS)

AF:

0.0190

AC:

AN:

210

South Asian (SAS)

AF:

0.0139

AC:

AN:

144

European-Finnish (FIN)

AF:

0.0407

AC:

AN:

172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0348

AC:

AN:

2554

Other (OTH)

AF:

0.0484

AC:

AN:

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.317

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

DANN

Benign

0.35

PhyloP100

-2.0

PromoterAI

-0.0032

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over