Genetic Variant KRTAP21-3:p.Gly34Ser (chr21-30718660-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164435.1(KRTAP21-3):c.100G>A(p.Gly34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,548,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

KRTAP21-3
NM_001164435.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00400

Variant links:

Genes affected

KRTAP21-3 (HGNC:34216): (keratin associated protein 21-3) Predicted to be located in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP21-3 links:

LOC105372773 (HGNC:):

LOC105372773 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08007428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP21-3	NM_001164435.1 link	c.100G>A	p.Gly34Ser	missense_variant	Exon 1 of 1	ENST00000444335.1	NP_001157907.1	Q3LHN1
LOC105372773	XR_937655.3 link	n.407+3440G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP21-3	ENST00000444335.1 link	c.100G>A	p.Gly34Ser	missense_variant	Exon 1 of 1	6	NM_001164435.1	ENSP00000404517.1		Q3LHN1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000131

AC:

AN:

152958

Hom.:

AF XY:

0.000173

AC XY:

AN XY:

81030

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000427

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000208

AC:

291

AN:

1396414

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

146

AN XY:

688596

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

Gnomad4 AMR exome

AF:

0.000569

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000238

Gnomad4 OTH exome

AF:

0.000225

GnomAD4 genome

AF:

0.000184

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000192

Hom.:

Bravo

AF:

0.000234

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.100G>A (p.G34S) alteration is located in exon 1 (coding exon 1) of the KRTAP21-3 gene. This alteration results from a G to A substitution at nucleotide position 100, causing the glycine (G) at amino acid position 34 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.054

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.34

M_CAP

Benign

0.0097

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.026

Sift4G

Benign

0.38

Vest4

0.19

MVP

0.030

ClinPred

0.20

GERP RS

-1.1

Varity_R

0.26

gMVP

0.0031

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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