chr5-147399170-T-C

Position:

• chr5-147399170-T-C

Variant summary

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

The NM_001197294.2(DPYSL3):​c.1535A>G​(p.Lys512Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DPYSL3 NM_001197294.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.00

Genes affected

DPYSL3 (HGNC:3015): (dihydropyrimidinase like 3) Enables filamin binding activity. Predicted to be involved in several processes, including actin filament organization; regulation of plasma membrane bounded cell projection organization; and response to axon injury. Predicted to act upstream of or within nervous system development. Predicted to be located in several cellular components, including cell body; growth cone; and lamellipodium. Predicted to be part of filamentous actin. Predicted to be active in synapse. Predicted to colocalize with exocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

STK32A (HGNC:):

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, 0.967

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPYSL3	NM_001197294.2	c.1535A>G	p.Lys512Arg	missense_variant	11/14	ENST00000343218.10
DPYSL3	NM_001387.3	c.1193A>G	p.Lys398Arg	missense_variant	11/14
DPYSL3	XM_011537574.3	c.1181A>G	p.Lys394Arg	missense_variant	11/14
STK32A	XM_011537577.3	c.1163-2197T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYSL3	ENST00000343218.10	c.1535A>G	p.Lys512Arg	missense_variant	11/14	1	NM_001197294.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.1535A>G (p.K512R) alteration is located in exon 11 (coding exon 11) of the DPYSL3 gene. This alteration results from a A to G substitution at nucleotide position 1535, causing the lysine (K) at amino acid position 512 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.59	D;.
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Pathogenic	0.63	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.4	H;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.88
MutPred		0.89		Gain of methylation at K398 (P = 0.0687);.;
MVP		0.91
MPC		1.3
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.83
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.40		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-146778733;