rs924978478

Variant names:

• chr14-20429334-C-G
• rs924978478
• NM_001365790.2:c.1909G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-20429334-C-G
• chr14-20429334-C-A
• chr14-20429334-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365790.2(KLHL33):​c.1909G>C​(p.Val637Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000058 in 1,551,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: KLHL33 NM_001365790.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.680
• Publications: 0 publications found

Genes affected

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

ENSG00000291038 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25113803).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365790.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL33	NM_001365790.2	MANE Select	c.1909G>C	p.Val637Leu	missense	Exon 5 of 5	NP_001352719.1	A0A1B0GUB7
	KLHL33	NM_001109997.3		c.1117G>C	p.Val373Leu	missense	Exon 4 of 4	NP_001103467.2	A6NCF5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL33	ENST00000636854.3	TSL:5 MANE Select	c.1909G>C	p.Val637Leu	missense	Exon 5 of 5	ENSP00000490040.1	A0A1B0GUB7
	KLHL33	ENST00000344581.4	TSL:5	c.1117G>C	p.Val373Leu	missense	Exon 4 of 4	ENSP00000341549.4	A6NCF5
	KLHL33	ENST00000637228.1	TSL:5	c.*68G>C		3_prime_UTR	Exon 4 of 4	ENSP00000489731.1	A0A1B0GTK0

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000500 AC: 7 AN: 1399414 Hom.: 0 Cov.: 37 AF XY: 0.00000290 AC XY: 2 AN XY: 690208

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078982

Other (OTH) AF: 0.0000862 AC: 5 AN: 58006

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.14
DANN	Benign	0.80
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.68
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.41
Sift	Benign	0.10	T
Sift4G	Benign	0.096	T
Polyphen		0.014	B
Vest4		0.32
MutPred		0.62		Gain of sheet (P = 0.0827)
MVP		0.048
ClinPred		0.39	T
GERP RS		-3.5
Varity_R		0.087
gMVP		0.42
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs924978478; hg19: chr14-20897493;