rs530644820

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020866.3(KLHL1):​c.1891G>T​(p.Ala631Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,284 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A631T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KLHL1
NM_020866.3 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.92

Publications

0 publications found
Variant links:
Genes affected
KLHL1 (HGNC:6352): (kelch like family member 1) The KLHL1 protein belongs to a family of actin-organizing proteins related to Drosophila Kelch (Nemes et al., 2000 [PubMed 10888605]).[supplied by OMIM, Feb 2010]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KLHL1NM_020866.3 linkc.1891G>T p.Ala631Ser missense_variant Exon 9 of 11 ENST00000377844.9 NP_065917.1 Q9NR64Q8TBJ7
KLHL1NM_001286725.2 linkc.1708G>T p.Ala570Ser missense_variant Exon 8 of 10 NP_001273654.1 Q9NR64F5H1J3Q8TBJ7B7Z3I8
KLHL1XM_017020678.3 linkc.1372G>T p.Ala458Ser missense_variant Exon 9 of 11 XP_016876167.1
KLHL1XM_017020679.2 linkc.1222G>T p.Ala408Ser missense_variant Exon 9 of 11 XP_016876168.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KLHL1ENST00000377844.9 linkc.1891G>T p.Ala631Ser missense_variant Exon 9 of 11 1 NM_020866.3 ENSP00000367075.4 Q9NR64
KLHL1ENST00000545028.2 linkc.1708G>T p.Ala570Ser missense_variant Exon 8 of 10 2 ENSP00000439602.2 F5H1J3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251010
AF XY:
0.00000737
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS 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:
0.00000137
AC:
2
AN:
1461284
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726946
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33452
American (AMR)
AF:
0.0000224
AC:
1
AN:
44654
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26114
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111572
Other (OTH)
AF:
0.00
AC:
0
AN:
60376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.44
T;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.026
D
MetaRNN
Uncertain
0.45
T;T
MetaSVM
Uncertain
-0.061
T
MutationAssessor
Benign
0.77
N;.
PhyloP100
3.9
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-2.1
N;.
REVEL
Uncertain
0.42
Sift
Benign
0.17
T;.
Sift4G
Benign
0.12
T;T
Polyphen
0.87
P;.
Vest4
0.47
MutPred
0.51
Gain of catalytic residue at K635 (P = 6e-04);.;
MVP
0.82
MPC
0.26
ClinPred
0.76
D
GERP RS
5.8
Varity_R
0.13
gMVP
0.19
Mutation Taster
=79/21
polymorphism

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

Other links and lift over

dbSNP: rs530644820; hg19: chr13-70293625; API