6-97085306-C-A

Variant names:

• chr6-97085306-C-A
• rs771880644
• NM_052904.4:c.592C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052904.4(KLHL32):​c.592C>A​(p.Arg198Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R198H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: KLHL32 NM_052904.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.92
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38545412).

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.592C>A	p.Arg198Ser	missense	Exon 6 of 11	NP_443136.2	Q96NJ5-1
	KLHL32	NM_001323252.2		c.592C>A	p.Arg198Ser	missense	Exon 7 of 12	NP_001310181.1	Q96NJ5-1
	KLHL32	NM_001286250.2		c.484C>A	p.Arg162Ser	missense	Exon 5 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.592C>A	p.Arg198Ser	missense	Exon 6 of 11	ENSP00000358265.4	Q96NJ5-1
	KLHL32	ENST00000620278.1	TSL:1	c.-74C>A		5_prime_UTR	Exon 5 of 9	ENSP00000482012.1	A0A087WYQ8
	KLHL32	ENST00000951639.1		c.592C>A	p.Arg198Ser	missense	Exon 7 of 12	ENSP00000621698.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152142 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74316

African (AFR) AF: 0.0000483 AC: 2 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.11
Sift	Benign	0.83	T
Sift4G	Uncertain	0.014	D
Polyphen		0.0030	B
Vest4		0.60
MutPred		0.40		Gain of disorder (P = 0.0469)
MVP		0.41
MPC		0.88
ClinPred		0.90	D
GERP RS		6.1
Varity_R		0.25
gMVP		0.49
Mutation Taster		=54/46	polymorphism

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

dbSNP: rs771880644; hg19: chr6-97533182;