rs372157970

Variant names:

• chr14-20429088-G-A
• rs372157970
• NM_001365790.2:c.2155C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-20429088-G-A
• chr14-20429088-G-C
• chr14-20429088-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001365790.2(KLHL33):​c.2155C>T​(p.His719Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,399,346 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: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: KLHL33 NM_001365790.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.53

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL33	NM_001365790.2	c.2155C>T	p.His719Tyr	missense_variant	Exon 5 of 5	ENST00000636854.3	NP_001352719.1
KLHL33	NM_001109997.3	c.1363C>T	p.His455Tyr	missense_variant	Exon 4 of 4		NP_001103467.2
KLHL33	XM_011536450.3	c.2155C>T	p.His719Tyr	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.2155C>T	p.His719Tyr	missense_variant	Exon 5 of 5	5	NM_001365790.2	ENSP00000490040.1
KLHL33	ENST00000344581.4	c.1363C>T	p.His455Tyr	missense_variant	Exon 4 of 4	5		ENSP00000341549.4
KLHL33	ENST00000637228	c.*314C>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000489731.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000641 AC: 1 AN: 156012 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82720

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000166

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 18 AN: 1399346 Hom.: 0 Cov.: 37 AF XY: 0.0000159 AC XY: 11 AN XY: 690182

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000112

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000120

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	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.4	.;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0040	.;D
Sift4G	Uncertain	0.0080	.;D
Polyphen		1.0	.;D
Vest4		0.69
MutPred		0.73		.;Loss of disorder (P = 0.0412);
MVP		0.33
ClinPred		0.87	D
GERP RS		5.4
Varity_R		0.40
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

LitVar

Other links and lift over

dbSNP: rs372157970; hg19: chr14-20897247;