1-161099046-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHDC9 NM_152366.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 40 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08610776).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152366.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC9	NM_152366.5	MANE Select	c.511A>T	p.Ser171Cys	missense	Exon 1 of 4	NP_689579.3
	KLHDC9	NM_001007255.3		c.511A>T	p.Ser171Cys	missense	Exon 1 of 4	NP_001007256.1
	KLHDC9	NR_033385.2		n.425A>T		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC9	ENST00000368011.9	TSL:1 MANE Select	c.511A>T	p.Ser171Cys	missense	Exon 1 of 4	ENSP00000356990.4
	KLHDC9	ENST00000392192.6	TSL:1	c.511A>T	p.Ser171Cys	missense	Exon 1 of 4	ENSP00000376030.2
	KLHDC9	ENST00000917942.1		c.511A>T	p.Ser171Cys	missense	Exon 1 of 4	ENSP00000588001.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 21183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L
PhyloP100		-1.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.10
Sift	Benign	0.052	T
Sift4G	Uncertain	0.045	D
Polyphen		0.46	P
Vest4		0.24
MutPred		0.40		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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs11576830; hg19: chr1-161068836;