10-132198418-C-G

Variant names:

• chr10-132198418-C-G
• NM_006426.3:c.625C>G

Variant summary

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

The NM_006426.3(DPYSL4):​c.625C>G​(p.Gln209Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,460 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DPYSL4 NM_006426.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39

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.625C>G	p.Gln209Glu	missense_variant	Exon 7 of 14	ENST00000338492.9	NP_006417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL4	ENST00000338492.9	c.625C>G	p.Gln209Glu	missense_variant	Exon 7 of 14	1	NM_006426.3	ENSP00000339850.3
DPYSL4	ENST00000368627.1	c.391-433C>G		intron_variant	Intron 4 of 9	5		ENSP00000357616.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453460 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722238

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.625C>G (p.Q209E) alteration is located in exon 7 (coding exon 7) of the DPYSL4 gene. This alteration results from a C to G substitution at nucleotide position 625, causing the glutamine (Q) at amino acid position 209 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	0.12
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.42
Sift	Benign	0.16	T
Sift4G	Benign	0.23	T
Polyphen		0.21	B
Vest4		0.58
MutPred		0.57		Gain of disorder (P = 0.0514);
MVP		0.92
MPC		0.34
ClinPred		0.79	D
GERP RS		2.8
Varity_R		0.46
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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: chr10-134011922;