rs1045252007

Variant names:

• chr14-20429030-C-G
• rs1045252007
• NM_001365790.2:c.2213G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-20429030-C-G
• chr14-20429030-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001365790.2(KLHL33):​c.2213G>C​(p.Ser738Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,396 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S738N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: KLHL33 NM_001365790.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL33	NM_001365790.2	c.2213G>C	p.Ser738Thr	missense_variant	Exon 5 of 5	ENST00000636854.3	NP_001352719.1
KLHL33	NM_001109997.3	c.1421G>C	p.Ser474Thr	missense_variant	Exon 4 of 4		NP_001103467.2
KLHL33	XM_011536450.3	c.2213G>C	p.Ser738Thr	missense_variant	Exon 5 of 5		XP_011534752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL33	ENST00000636854.3	c.2213G>C	p.Ser738Thr	missense_variant	Exon 5 of 5	5	NM_001365790.2	ENSP00000490040.1
KLHL33	ENST00000344581.4	c.1421G>C	p.Ser474Thr	missense_variant	Exon 4 of 4	5		ENSP00000341549.4
KLHL33	ENST00000637228	c.*372G>C		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000489731.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399396 Hom.: 0 Cov.: 37 AF XY: 0.00000145 AC XY: 1 AN XY: 690200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.2	.;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0040	.;D
Sift4G	Pathogenic	0.0	.;D
Polyphen		1.0	.;D
Vest4		0.29
MutPred		0.77		.;Loss of catalytic residue at L470 (P = 0.2562);
MVP		0.30
ClinPred		0.91	D
GERP RS		5.2
Varity_R		0.29
gMVP		0.40

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: rs1045252007; hg19: chr14-20897189;