6-97113908-C-G

Variant names:

• chr6-97113908-C-G
• NM_052904.4:c.753C>G
• KLHL32 p.Val251Val

Variant summary

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

The NM_001323256.2(KLHL32):​c.832C>G​(p.Pro278Ala) 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. 13/17 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. P278S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHL32 NM_001323256.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 0 publications found

Genes affected

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

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=0.1163367).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323256.2. 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.753C>G	p.Val251Val	synonymous	Exon 7 of 11	NP_443136.2	Q96NJ5-1
	KLHL32	NM_001323256.2		c.832C>G	p.Pro278Ala	missense	Exon 8 of 8	NP_001310185.1
	KLHL32	NM_001323252.2		c.753C>G	p.Val251Val	synonymous	Exon 8 of 12	NP_001310181.1	Q96NJ5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL32	ENST00000369261.9	TSL:2 MANE Select	c.753C>G	p.Val251Val	synonymous	Exon 7 of 11	ENSP00000358265.4	Q96NJ5-1
	KLHL32	ENST00000620278.1	TSL:1	c.-38-13496C>G		intron	N/A	ENSP00000482012.1	A0A087WYQ8
	KLHL32	ENST00000447886.1	TSL:3	c.520C>G	p.Pro174Ala	missense	Exon 4 of 4	ENSP00000389310.1	Q5THS9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	1.7
DANN	Benign	0.51
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.015
PROVEAN	Benign	1.1	N
REVEL	Benign	0.034
Sift	Pathogenic	0.0	D
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-97561784;