Variant 1-161099043-C-T 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_152366.5(KLHDC9):c.508C>T(p.Pro170Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24095568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLHDC9	NM_152366.5 linkuse as main transcript	c.508C>T	p.Pro170Ser	missense_variant	1/4	ENST00000368011.9	NP_689579.3
KLHDC9	NM_001007255.3 linkuse as main transcript	c.508C>T	p.Pro170Ser	missense_variant	1/4		NP_001007256.1
KLHDC9	NR_033385.2 linkuse as main transcript	n.422C>T		non_coding_transcript_exon_variant	2/5
KLHDC9	NR_033386.2 linkuse as main transcript	n.422C>T		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC9	ENST00000368011.9 linkuse as main transcript	c.508C>T	p.Pro170Ser	missense_variant	1/4	1	NM_152366.5	ENSP00000356990	P1	Q8NEP7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444696

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718930

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 01, 2023

The c.508C>T (p.P170S) alteration is located in exon 1 (coding exon 1) of the KLHDC9 gene. This alteration results from a C to T substitution at nucleotide position 508, causing the proline (P) at amino acid position 170 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

0.0093

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0029

T;.

Eigen

Benign

0.17

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

0.90

D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.21

Sift

Benign

0.24

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.89

P;D

Vest4

0.38

MutPred

0.27

Gain of phosphorylation at P170 (P = 0.0422);Gain of phosphorylation at P170 (P = 0.0422);

MVP

0.56

MPC

0.41

ClinPred

0.82

GERP RS

5.0

Varity_R

0.085

gMVP

0.69

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over