Variant chr21-44551387-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198693.4(KRTAP10-2):c.72G>C(p.Glu24Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,034 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

KRTAP10-2
NM_198693.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

Variant links:

Genes affected

KRTAP10-2 (HGNC:22967): (keratin associated protein 10-2) This gene encodes a member of the high sulfur-type keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. This gene is located in a cluster of similar genes on 21q22.3. Alternatively-spliced transcript variants have been identified. [provided by RefSeq, Jan 2015]

KRTAP10-2 links:

TSPEAR (HGNC:1268): (thrombospondin type laminin G domain and EAR repeats) This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

TSPEAR links:

KRTAP10-2 (HGNC:):

KRTAP10-2 links:

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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=0.2109099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP10-2	NM_198693.4 linkuse as main transcript	c.72G>C	p.Glu24Asp	missense_variant	1/1	ENST00000391621.1	NP_941966.1	P60368-1
TSPEAR	NM_144991.3 linkuse as main transcript	c.303+16398G>C		intron_variant		ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 linkuse as main transcript	c.99+16398G>C		intron_variant			NP_001258966.1	Q8WU66
KRTAP10-2	NR_130165.2 linkuse as main transcript	n.119G>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP10-2	ENST00000391621.1 linkuse as main transcript	c.72G>C	p.Glu24Asp	missense_variant	1/1	6	NM_198693.4	ENSP00000375479.1		P60368-1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.303+16398G>C		intron_variant		1	NM_144991.3	ENSP00000321987.4		Q8WU66-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251146

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461034

Hom.:

Cov.:

159

AF XY:

0.00000275

AC XY:

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

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

Feb 12, 2024

The c.72G>C (p.E24D) alteration is located in exon 1 (coding exon 1) of the KRTAP10-2 gene. This alteration results from a G to C substitution at nucleotide position 72, causing the glutamic acid (E) at amino acid position 24 to be replaced by an aspartic acid (D). 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

0.19

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.78

M_CAP

Benign

0.0041

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.14

Sift

Benign

0.11

Sift4G

Benign

0.061

Polyphen

1.0

Vest4

0.27

MutPred

0.45

Gain of glycosylation at S25 (P = 0.1624);

MVP

0.17

MPC

0.19

ClinPred

0.83

GERP RS

3.3

Varity_R

0.11

gMVP

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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