6-97114398-A-G

Position:

• chr6-97114398-A-G

Variant summary

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

The NM_052904.4(KLHL32):​c.1243A>G​(p.Thr415Ala) variant causes a missense change. 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: 4.38

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/exons	MANE	Protein	UniProt
KLHL32	NM_052904.4	c.1243A>G	p.Thr415Ala	missense_variant	7/11	ENST00000369261.9	NP_443136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL32	ENST00000369261.9	c.1243A>G	p.Thr415Ala	missense_variant	7/11	2	NM_052904.4	ENSP00000358265	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.1243A>G (p.T415A) alteration is located in exon 7 (coding exon 6) of the KLHL32 gene. This alteration results from a A to G substitution at nucleotide position 1243, causing the threonine (T) at amino acid position 415 to be replaced by an alanine (A). 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	0.21
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;.;T
Eigen	Benign	0.0042
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.7	.;.;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.036	.;.;B
Vest4		0.55
MutPred		0.53		.;.;Loss of phosphorylation at T415 (P = 0.0404);
MVP		0.74
MPC		0.47
ClinPred		0.84	D
GERP RS		5.7
Varity_R		0.22
gMVP		0.54

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: chr6-97562274;