chr2-238141101-C-T

Variant names:

• chr2-238141101-C-T
• rs766734319
• NM_198582.4:c.347C>T

Variant summary

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

The NM_198582.4(KLHL30):​c.347C>T​(p.Pro116Leu) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P116H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: KLHL30 NM_198582.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.94

Genes affected

KLHL30 (HGNC:24770): (kelch like family member 30)

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, 0.791

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL30	NM_198582.4	c.347C>T	p.Pro116Leu	missense_variant	Exon 2 of 8	ENST00000409223.2	NP_940984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL30	ENST00000409223.2	c.347C>T	p.Pro116Leu	missense_variant	Exon 2 of 8	5	NM_198582.4	ENSP00000386389.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	0.76	N
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.022	D
Polyphen		0.99	D
Vest4		0.51
MutPred		0.73		Gain of MoRF binding (P = 0.0587);
MVP		0.85
MPC		0.61
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.54
gMVP		0.55

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

LitVar

Other links and lift over

dbSNP: rs766734319; hg19: chr2-239049742; COSMIC: COSV105190827;