2-238141116-T-C

Variant names:

• chr2-238141116-T-C
• NM_198582.4:c.362T>C

Variant summary

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

The NM_198582.4(KLHL30):​c.362T>C​(p.Val121Ala) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: KLHL30 NM_198582.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44
• Publications: 0 publications found

Genes affected

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

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=0.14824897).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198582.4. 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
	KLHL30	NM_198582.4	MANE Select	c.362T>C	p.Val121Ala	missense	Exon 2 of 8	NP_940984.3	Q0D2K2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL30	ENST00000409223.2	TSL:5 MANE Select	c.362T>C	p.Val121Ala	missense	Exon 2 of 8	ENSP00000386389.1	Q0D2K2
	KLHL30	ENST00000964872.1		c.362T>C	p.Val121Ala	missense	Exon 2 of 7	ENSP00000634931.1
	KLHL30	ENST00000964871.1		c.362T>C	p.Val121Ala	missense	Exon 2 of 7	ENSP00000634930.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 77

GnomAD4 genome Cov.: 34

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	Benign	0.18
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.56
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.49	N
PhyloP100		3.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.20	N
REVEL	Benign	0.093
Sift	Benign	1.0	T
Sift4G	Benign	0.22	T
Polyphen		0.14	B
Vest4		0.22
MutPred		0.56		Loss of methylation at K120 (P = 0.061)
MVP		0.55
MPC		0.31
ClinPred		0.17	T
GERP RS		3.3
Varity_R		0.097
gMVP		0.49
Mutation Taster		=50/50

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

Other links and lift over

hg19: chr2-239049757;