1-161098674-C-T

Variant names:

• chr1-161098674-C-T
• rs147391231
• NM_152366.5:c.139C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152366.5(KLHDC9):​c.139C>T​(p.Leu47Leu) variant causes a synonymous 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. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=0.804 with no splicing effect.

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.139C>T	p.Leu47Leu	synonymous	Exon 1 of 4	NP_689579.3
	KLHDC9	NM_001007255.3		c.139C>T	p.Leu47Leu	synonymous	Exon 1 of 4	NP_001007256.1	Q8NEP7-2
	KLHDC9	NR_033385.2		n.53C>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.139C>T	p.Leu47Leu	synonymous	Exon 1 of 4	ENSP00000356990.4	Q8NEP7-1
	KLHDC9	ENST00000392192.6	TSL:1	c.139C>T	p.Leu47Leu	synonymous	Exon 1 of 4	ENSP00000376030.2	Q8NEP7-2
	KLHDC9	ENST00000917942.1		c.139C>T	p.Leu47Leu	synonymous	Exon 1 of 4	ENSP00000588001.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		0.80
PromoterAI		0.0086	Neutral
Mutation Taster		=100/0	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: rs147391231; hg19: chr1-161068464;