chr13-69839032-G-C

Variant names:

• chr13-69839032-G-C
• NM_020866.3:c.1358C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020866.3(KLHL1):​c.1358C>G​(p.Pro453Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: KLHL1 NM_020866.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.94

Genes affected

KLHL1 (HGNC:6352): (kelch like family member 1) The KLHL1 protein belongs to a family of actin-organizing proteins related to Drosophila Kelch (Nemes et al., 2000 [PubMed 10888605]).[supplied by OMIM, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL1	NM_020866.3	c.1358C>G	p.Pro453Arg	missense_variant	Exon 6 of 11	ENST00000377844.9	NP_065917.1
KLHL1	NM_001286725.2	c.1175C>G	p.Pro392Arg	missense_variant	Exon 5 of 10		NP_001273654.1
KLHL1	XM_017020678.3	c.839C>G	p.Pro280Arg	missense_variant	Exon 6 of 11		XP_016876167.1
KLHL1	XM_017020679.2	c.689C>G	p.Pro230Arg	missense_variant	Exon 6 of 11		XP_016876168.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL1	ENST00000377844.9	c.1358C>G	p.Pro453Arg	missense_variant	Exon 6 of 11	1	NM_020866.3	ENSP00000367075.4
KLHL1	ENST00000545028.2	c.1175C>G	p.Pro392Arg	missense_variant	Exon 5 of 10	2		ENSP00000439602.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Pathogenic	3.2	M;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-7.3	D;.
REVEL	Uncertain	0.61
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;.
Vest4		0.82
MutPred		0.39		Gain of catalytic residue at R450 (P = 0.0089);.;
MVP		0.93
MPC		0.38
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.79
gMVP		0.50

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-70413164;