rs568020384

Variant names:

• chr10-132192662-A-C
• rs568020384
• NM_006426.3:c.133A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-132192662-A-C
• chr10-132192662-A-G

Variant summary

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

The NM_006426.3(DPYSL4):​c.133A>C​(p.Ile45Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I45V) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: DPYSL4 NM_006426.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.05

Genes affected

DPYSL4 (HGNC:3016): (dihydropyrimidinase like 4) Enables filamin binding activity. Predicted to be involved in nervous system development. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
DPYSL4	NM_006426.3	c.133A>C	p.Ile45Leu	missense_variant	Exon 3 of 14	ENST00000338492.9	NP_006417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL4	ENST00000338492.9	c.133A>C	p.Ile45Leu	missense_variant	Exon 3 of 14	1	NM_006426.3	ENSP00000339850.3
DPYSL4	ENST00000493882.1	n.290A>C		non_coding_transcript_exon_variant	Exon 4 of 6	3
DPYSL4	ENST00000493927.5	n.457A>C		non_coding_transcript_exon_variant	Exon 4 of 4	3
DPYSL4	ENST00000368627.1	c.-99A>C		upstream_gene_variant		5		ENSP00000357616.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74336

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000540 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Benign	0.79	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.4	N
REVEL	Pathogenic	0.70
Sift	Benign	0.15	T
Sift4G	Benign	0.12	T
Polyphen		0.92	P
Vest4		0.56
MutPred		0.67		Gain of catalytic residue at I45 (P = 0.2402);
MVP		0.88
MPC		0.28
ClinPred		0.87	D
GERP RS		4.9
Varity_R		0.36
gMVP		0.89

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: rs568020384; hg19: chr10-134006166;