21-44600709-G-A

Variant summary

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

The NM_198689.3(KRTAP10-7):​c.88G>A​(p.Asp30Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,613,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

KRTAP10-7
NM_198689.3 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.298
Variant links:
Genes affected
KRTAP10-7 (HGNC:22970): (keratin associated protein 10-7) Enables identical protein binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
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]

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=0.07338348).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KRTAP10-7NM_198689.3 linkc.88G>A p.Asp30Asn missense_variant 1/1 ENST00000609664.2 NP_941962.1 P60409
TSPEARNM_144991.3 linkc.83-32704C>T intron_variant ENST00000323084.9 NP_659428.2 Q8WU66-1
TSPEARNM_001272037.2 linkc.-122-32704C>T intron_variant NP_001258966.1 Q8WU66

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KRTAP10-7ENST00000609664.2 linkc.88G>A p.Asp30Asn missense_variant 1/16 NM_198689.3 ENSP00000476821.1 P60409
TSPEARENST00000323084.9 linkc.83-32704C>T intron_variant 1 NM_144991.3 ENSP00000321987.4 Q8WU66-1
TSPEARENST00000642437.1 linkn.*28-32704C>T intron_variant ENSP00000496535.1 A0A2R8YFK6

Frequencies

GnomAD3 genomes
AF:
0.0000660
AC:
10
AN:
151444
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000734
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000289
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000815
AC:
20
AN:
245312
Hom.:
0
AF XY:
0.0000752
AC XY:
10
AN XY:
132976
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000472
Gnomad NFE exome
AF:
0.000162
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000140
AC:
205
AN:
1461708
Hom.:
0
Cov.:
32
AF XY:
0.000136
AC XY:
99
AN XY:
727144
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
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:
0.0000187
Gnomad4 NFE exome
AF:
0.000172
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000660
AC:
10
AN:
151444
Hom.:
0
Cov.:
32
AF XY:
0.0000676
AC XY:
5
AN XY:
73976
show subpopulations
Gnomad4 AFR
AF:
0.0000734
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000289
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000642
ExAC
AF:
0.0000827
AC:
10

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 submitterclinical testingAmbry GeneticsFeb 15, 2023The c.88G>A (p.D30N) alteration is located in exon 1 (coding exon 1) of the KRTAP10-7 gene. This alteration results from a G to A substitution at nucleotide position 88, causing the aspartic acid (D) at amino acid position 30 to be replaced by an asparagine (N). 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
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.065
T
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.073
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.0
M
PrimateAI
Benign
0.25
T
Sift4G
Benign
0.14
T
Vest4
0.12
MVP
0.37
ClinPred
0.046
T
GERP RS
-0.0015
Varity_R
0.042
gMVP
0.023

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.

Other links and lift over

dbSNP: rs782441627; hg19: chr21-46020609; API