chr1-161098621-C-T

Variant names:

• chr1-161098621-C-T
• rs747305220
• NM_152366.5:c.86C>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.86C>T​(p.Ala29Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,608,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: KLHDC9 NM_152366.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34
• 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: 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=0.10595822).

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.86C>T	p.Ala29Val	missense	Exon 1 of 4	NP_689579.3
	KLHDC9	NM_001007255.3		c.86C>T	p.Ala29Val	missense	Exon 1 of 4	NP_001007256.1	Q8NEP7-2
	KLHDC9	NR_033385.2		n.45-45C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC9	ENST00000368011.9	TSL:1 MANE Select	c.86C>T	p.Ala29Val	missense	Exon 1 of 4	ENSP00000356990.4	Q8NEP7-1
	KLHDC9	ENST00000392192.6	TSL:1	c.86C>T	p.Ala29Val	missense	Exon 1 of 4	ENSP00000376030.2	Q8NEP7-2
	KLHDC9	ENST00000917942.1		c.86C>T	p.Ala29Val	missense	Exon 1 of 4	ENSP00000588001.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000544 AC: 13 AN: 239104 AF XY: 0.0000539

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00112

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000282 AC: 41 AN: 1456332 Hom.: 0 Cov.: 31 AF XY: 0.0000262 AC XY: 19 AN XY: 724124

African (AFR) AF: 0.00 AC: 0 AN: 33312

American (AMR) AF: 0.00 AC: 0 AN: 44052

Ashkenazi Jewish (ASJ) AF: 0.00131 AC: 34 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39368

South Asian (SAS) AF: 0.00 AC: 0 AN: 85268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109532

Other (OTH) AF: 0.0000999 AC: 6 AN: 60090

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000180 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.3
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.089
Sift	Benign	0.17	T
Sift4G	Benign	0.25	T
Polyphen		0.50	P
Vest4		0.35
MutPred		0.48		Loss of methylation at R28 (P = 0.0868)
MVP		0.19
MPC		0.43
ClinPred		0.093	T
GERP RS		2.0
PromoterAI		0.013	Neutral
Varity_R		0.10
gMVP		0.83
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs747305220; hg19: chr1-161068411;