dbSNP rs747305220: KLHDC9:p.Ala29Asp (chr1-161098621-C-A) – ACMG Classification: Uncertain_significance (2 pts)

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

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]

KLHDC9 links:

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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
KLHDC9	NM_152366.5 link	c.86C>A	p.Ala29Asp	missense_variant	Exon 1 of 4	ENST00000368011.9	NP_689579.3	Q8NEP7-1
KLHDC9	NM_001007255.3 link	c.86C>A	p.Ala29Asp	missense_variant	Exon 1 of 4		NP_001007256.1	Q8NEP7-2
KLHDC9	NR_033385.2 link	n.45-45C>A		intron_variant	Intron 1 of 4
KLHDC9	NR_033386.2 link	n.45-45C>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHDC9	ENST00000368011.9 link	c.86C>A	p.Ala29Asp	missense_variant	Exon 1 of 4	1	NM_152366.5	ENSP00000356990.4		Q8NEP7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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.:

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

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0094

T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Pathogenic

0.85

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over