Genetic Variant KRTAP5-7:p.Gly65Gly (chr11-71527495-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001012503.2(KRTAP5-7):c.195A>G(p.Gly65Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,387,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP5-7
NM_001012503.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0600

Variant links:

Genes affected

KRTAP5-7 (HGNC:23602): (keratin associated protein 5-7) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

BP6

Variant 11-71527495-A-G is Benign according to our data. Variant chr11-71527495-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3777844.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-7	NM_001012503.2 link	c.195A>G	p.Gly65Gly	synonymous_variant	Exon 1 of 1	ENST00000398536.6	NP_001012521.1	Q6L8G8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-7	ENST00000398536.6 link	c.195A>G	p.Gly65Gly	synonymous_variant	Exon 1 of 1	6	NM_001012503.2	ENSP00000417330.2		Q6L8G8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

105724

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000372

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000353

Gnomad EAS

AF:

0.000271

Gnomad SAS

AF:

0.000324

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000154

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000607

AC:

AN:

247194

Hom.:

AF XY:

0.0000747

AC XY:

AN XY:

133922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000400

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000187

AC:

AN:

1387736

Hom.:

Cov.:

144

AF XY:

0.0000246

AC XY:

AN XY:

691178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000152

Gnomad4 OTH exome

AF:

0.0000700

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000113

AC:

AN:

105736

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

50654

show subpopulations

Gnomad4 AFR

AF:

0.0000372

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000353

Gnomad4 EAS

AF:

0.000272

Gnomad4 SAS

AF:

0.000326

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000154

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00916

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KRTAP5-7: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.4

DANN

Benign

0.49

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