NM_052904.4:c.353C>A

Variant names:

• chr6-97064668-C-A
• rs760800476
• NM_052904.4:c.353C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_052904.4(KLHL32):​c.353C>A​(p.Ala118Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A118P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHL32 NM_052904.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.00
• Publications: 0 publications found

Genes affected

KLHL32 (HGNC:21221): (kelch like family member 32)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.88

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052904.4. 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
	KLHL32	NM_052904.4	MANE Select	c.353C>A	p.Ala118Glu	missense	Exon 5 of 11	NP_443136.2	Q96NJ5-1
	KLHL32	NM_001323252.2		c.353C>A	p.Ala118Glu	missense	Exon 6 of 12	NP_001310181.1	Q96NJ5-1
	KLHL32	NM_001286250.2		c.245C>A	p.Ala82Glu	missense	Exon 4 of 10	NP_001273179.1	Q96NJ5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL32	ENST00000369261.9	TSL:2 MANE Select	c.353C>A	p.Ala118Glu	missense	Exon 5 of 11	ENSP00000358265.4	Q96NJ5-1
	KLHL32	ENST00000620278.1	TSL:1	c.-313C>A		5_prime_UTR	Exon 4 of 9	ENSP00000482012.1	A0A087WYQ8
	KLHL32	ENST00000951639.1		c.353C>A	p.Ala118Glu	missense	Exon 6 of 12	ENSP00000621698.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		7.0
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.73		Gain of disorder (P = 0.2233)
MVP		0.89
MPC		1.3
ClinPred		1.0	D
GERP RS		5.5
PromoterAI		0.0063	Neutral
Varity_R		0.89
gMVP		0.90
Mutation Taster		=67/233	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs760800476; hg19: chr6-97512544;