rs747305220

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152366.5(KLHDC9):​c.86C>A​(p.Ala29Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,332 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. A29V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KLHDC9
NM_152366.5 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.34
Variant links:
Genes affected
KLHDC9 (HGNC:28489): (kelch domain containing 9) Enables cyclin binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
KLHDC9NM_152366.5 linkc.86C>A p.Ala29Asp missense_variant Exon 1 of 4 ENST00000368011.9 NP_689579.3 Q8NEP7-1
KLHDC9NM_001007255.3 linkc.86C>A p.Ala29Asp missense_variant Exon 1 of 4 NP_001007256.1 Q8NEP7-2
KLHDC9NR_033385.2 linkn.45-45C>A intron_variant Intron 1 of 4
KLHDC9NR_033386.2 linkn.45-45C>A intron_variant Intron 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KLHDC9ENST00000368011.9 linkc.86C>A p.Ala29Asp missense_variant Exon 1 of 4 1 NM_152366.5 ENSP00000356990.4 Q8NEP7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1456332
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
724124
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.78
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0094
T;.
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.14
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.060
D
MetaRNN
Uncertain
0.65
D;D
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-2.4
N;D
REVEL
Uncertain
0.42
Sift
Benign
0.043
D;D
Sift4G
Uncertain
0.023
D;D
Polyphen
0.78
P;P
Vest4
0.69
MutPred
0.58
Loss of MoRF binding (P = 0.0393);Loss of MoRF binding (P = 0.0393);
MVP
0.45
MPC
1.2
ClinPred
0.84
D
GERP RS
2.0
Varity_R
0.33
gMVP
0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-161068411; API