Variant 11-71527716-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001012503.2(KRTAP5-7):c.416C>G(p.Ser139Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,199,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000023 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP5-7
NM_001012503.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.19

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038061857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-7	NM_001012503.2 linkuse as main transcript	c.416C>G	p.Ser139Cys	missense_variant	1/1	ENST00000398536.6	NP_001012521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-7	ENST00000398536.6 linkuse as main transcript	c.416C>G	p.Ser139Cys	missense_variant	1/1		NM_001012503.2	ENSP00000417330	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

137082

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000725

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000221

Gnomad SAS

AF:

0.000494

Gnomad FIN

AF:

0.000209

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000172

Gnomad OTH

AF:

0.00109

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1199220

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

600338

show subpopulations

Gnomad4 AFR exome

AF:

0.000423

Gnomad4 AMR exome

AF:

0.0000232

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000209

Gnomad4 NFE exome

AF:

0.0000113

Gnomad4 OTH exome

AF:

0.0000773

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000277

AC:

AN:

137166

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

AN XY:

66764

show subpopulations

Gnomad4 AFR

AF:

0.000284

Gnomad4 AMR

AF:

0.000724

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000221

Gnomad4 SAS

AF:

0.000495

Gnomad4 FIN

AF:

0.000209

Gnomad4 NFE

AF:

0.000172

Gnomad4 OTH

AF:

0.00107

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

The c.416C>G (p.S139C) alteration is located in exon 1 (coding exon 1) of the KRTAP5-7 gene. This alteration results from a C to G substitution at nucleotide position 416, causing the serine (S) at amino acid position 139 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.2

DANN

Benign

0.66

DEOGEN2

Benign

0.0054

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.022

M_CAP

Benign

0.00084

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.39

MutationTaster

Benign

1.0

PROVEAN

Benign

-1.7

REVEL

Benign

0.053

Sift

Benign

0.13

Sift4G

Benign

0.063

Polyphen

0.0

Vest4

0.12

MutPred

0.20

Loss of glycosylation at S139 (P = 0.0659);

MVP

0.043

MPC

0.011

ClinPred

0.035

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.071

gMVP

0.012

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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