6-96976085-G-A

Variant names:

• chr6-96976085-G-A
• NM_052904.4:c.112G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052904.4(KLHL32):​c.112G>A​(p.Asp38Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar 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: 7.77

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL32	NM_052904.4	c.112G>A	p.Asp38Asn	missense_variant	Exon 3 of 11	ENST00000369261.9	NP_443136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL32	ENST00000369261.9	c.112G>A	p.Asp38Asn	missense_variant	Exon 3 of 11	2	NM_052904.4	ENSP00000358265.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.112G>A (p.D38N) alteration is located in exon 3 (coding exon 2) of the KLHL32 gene. This alteration results from a G to A substitution at nucleotide position 112, causing the aspartic acid (D) at amino acid position 38 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	.;.;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.59	N;N;N;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.061	T;T;T;T
Polyphen		0.77	.;.;P;.
Vest4		0.69
MutPred		0.37		Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);
MVP		0.62
MPC		1.2
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.26
gMVP		0.50

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-97423961;