10-132194915-C-G

Variant names:

• chr10-132194915-C-G
• rs997362438
• NM_006426.3:c.384C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006426.3(DPYSL4):​c.384C>G​(p.Asp128Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,460,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: DPYSL4 NM_006426.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0680

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24582523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL4	NM_006426.3	c.384C>G	p.Asp128Glu	missense_variant	Exon 4 of 14	ENST00000338492.9	NP_006417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL4	ENST00000338492.9	c.384C>G	p.Asp128Glu	missense_variant	Exon 4 of 14	1	NM_006426.3	ENSP00000339850.3
DPYSL4	ENST00000368627.1	c.153C>G	p.Asp51Glu	missense_variant	Exon 2 of 10	5		ENSP00000357616.1
DPYSL4	ENST00000493882.1	n.541C>G		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1460280 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 726468

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: 0.0000243

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.384C>G (p.D128E) alteration is located in exon 4 (coding exon 4) of the DPYSL4 gene. This alteration results from a C to G substitution at nucleotide position 384, causing the aspartic acid (D) at amino acid position 128 to be replaced by a glutamic acid (E). 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	Benign	0.22
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.015	N
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.41
Sift	Benign	0.13	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.056	B;.
Vest4		0.33
MutPred		0.43		Gain of disorder (P = 0.1033);.;
MVP		0.79
MPC		0.27
ClinPred		0.38	T
GERP RS		3.6
Varity_R		0.27
gMVP		0.58

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: rs997362438; hg19: chr10-134008419;