1-161099046-A-T

Variant names:

• chr1-161099046-A-T
• rs11576830
• NM_152366.5:c.511A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152366.5(KLHDC9):​c.511A>T​(p.Ser171Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. S171R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHDC9 NM_152366.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

Genes affected

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

ACMG classification

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=0.08610776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC9	NM_152366.5	c.511A>T	p.Ser171Cys	missense_variant	Exon 1 of 4	ENST00000368011.9	NP_689579.3
KLHDC9	NM_001007255.3	c.511A>T	p.Ser171Cys	missense_variant	Exon 1 of 4		NP_001007256.1
KLHDC9	NR_033385.2	n.425A>T		non_coding_transcript_exon_variant	Exon 2 of 5
KLHDC9	NR_033386.2	n.425A>T		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHDC9	ENST00000368011.9	c.511A>T	p.Ser171Cys	missense_variant	Exon 1 of 4	1	NM_152366.5	ENSP00000356990.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.3
DANN	Benign	0.90
DEOGEN2	Benign	0.0087	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.086	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.10
Sift	Benign	0.052	T;D
Sift4G	Uncertain	0.045	D;D
Polyphen		0.46	P;P
Vest4		0.24
MutPred		0.40		Loss of MoRF binding (P = 0.0809);Loss of MoRF binding (P = 0.0809);
MVP		0.12
MPC		0.46
ClinPred		0.17	T
GERP RS		-7.1
Varity_R		0.066
gMVP		0.54

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

LitVar

Other links and lift over

dbSNP: rs11576830; hg19: chr1-161068836;