rs1037119585

Variant names:

• chr14-20429536-C-A
• rs1037119585
• NM_001365790.2:c.1807G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-20429536-C-A
• chr14-20429536-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001365790.2(KLHL33):​c.1807G>T​(p.Val603Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: KLHL33 NM_001365790.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40

Genes affected

KLHL33 (HGNC:31952): (kelch like family member 33)

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL33	NM_001365790.2	c.1807G>T	p.Val603Leu	missense_variant	Exon 4 of 5	ENST00000636854.3	NP_001352719.1
KLHL33	NM_001109997.3	c.1015G>T	p.Val339Leu	missense_variant	Exon 3 of 4		NP_001103467.2
KLHL33	XM_011536450.3	c.1807G>T	p.Val603Leu	missense_variant	Exon 4 of 5		XP_011534752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL33	ENST00000636854.3	c.1807G>T	p.Val603Leu	missense_variant	Exon 4 of 5	5	NM_001365790.2	ENSP00000490040.1
KLHL33	ENST00000637228.1	c.1807G>T	p.Val603Leu	missense_variant	Exon 3 of 4	5		ENSP00000489731.1
KLHL33	ENST00000344581.4	c.1015G>T	p.Val339Leu	missense_variant	Exon 3 of 4	5		ENSP00000341549.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000630 AC: 1 AN: 158804 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 83618

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000117

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400036 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 690490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.;T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Uncertain	2.6	.;.;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	.;.;N
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0020	.;.;D
Sift4G	Uncertain	0.024	.;.;D
Polyphen		1.0	.;.;D
Vest4		0.61
MutPred		0.90		.;.;Gain of phosphorylation at T341 (P = 0.2362);
MVP		0.33
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.90
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

LitVar

Other links and lift over

dbSNP: rs1037119585; hg19: chr14-20897695;