7-130096956-C-A

Variant names:

• chr7-130096956-C-A
• rs747421514
• NM_014997.4:c.202C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014997.4(KLHDC10):​c.202C>A​(p.Arg68Ser) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R68C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHDC10 NM_014997.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 2 publications found

Genes affected

KLHDC10 (HGNC:22194): (kelch domain containing 10) Enables ubiquitin ligase-substrate adaptor activity. Involved in ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in nucleoplasm. Is active in Cul2-RING ubiquitin ligase complex. [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=0.06863171).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014997.4. 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
	KLHDC10	NM_014997.4	MANE Select	c.202C>A	p.Arg68Ser	missense	Exon 2 of 10	NP_055812.1	Q6PID8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC10	ENST00000335420.10	TSL:1 MANE Select	c.202C>A	p.Arg68Ser	missense	Exon 2 of 10	ENSP00000334140.4	Q6PID8-1
	KLHDC10	ENST00000468226.1	TSL:3	c.-228C>A		5_prime_UTR	Exon 3 of 7	ENSP00000420034.1	C9JRX2
	KLHDC10	ENST00000851918.1		c.71-19489C>A		intron	N/A	ENSP00000521977.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.098
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.6
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.059
Sift	Benign	0.69	T
Sift4G	Benign	0.81	T
Polyphen		0.023	B
Vest4		0.31
MutPred		0.39		Gain of phosphorylation at R68 (P = 0.0346)
MVP		0.082
MPC		1.2
ClinPred		0.49	T
GERP RS		4.0
Varity_R		0.17
gMVP		0.45
Mutation Taster		=92/8	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: rs747421514; hg19: chr7-129736796;