10-132187095-G-C

Variant names:

• chr10-132187095-G-C
• rs753686812
• NM_006426.3:c.32G>C

Variant summary

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

The NM_006426.3(DPYSL4):​c.32G>C​(p.Arg11Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000773 in 1,294,446 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. R11Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: DPYSL4 NM_006426.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006426.3. 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
	DPYSL4	NM_006426.3	MANE Select	c.32G>C	p.Arg11Pro	missense	Exon 1 of 14	NP_006417.2	O14531

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL4	ENST00000338492.9	TSL:1 MANE Select	c.32G>C	p.Arg11Pro	missense	Exon 1 of 14	ENSP00000339850.3	O14531
	DPYSL4	ENST00000905073.1		c.32G>C	p.Arg11Pro	missense	Exon 1 of 14	ENSP00000575132.1
	DPYSL4	ENST00000905072.1		c.32G>C	p.Arg11Pro	missense	Exon 1 of 14	ENSP00000575131.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 7.73e-7 AC: 1 AN: 1294446 Hom.: 0 Cov.: 30 AF XY: 0.00000156 AC XY: 1 AN XY: 641234

African (AFR) AF: 0.00 AC: 0 AN: 26408

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20102

East Asian (EAS) AF: 0.00 AC: 0 AN: 26986

South Asian (SAS) AF: 0.00 AC: 0 AN: 76180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4952

European-Non Finnish (NFE) AF: 9.88e-7 AC: 1 AN: 1011916

Other (OTH) AF: 0.00 AC: 0 AN: 50216

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.050
Eigen_PC	Benign	0.058
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.16	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	-0.55	N
PhyloP100		1.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.59
Sift	Uncertain	0.016	D
Sift4G	Benign	0.098	T
Polyphen		0.47	P
Vest4		0.41
MutPred		0.49		Loss of MoRF binding (P = 2e-04)
MVP		0.88
MPC		0.66
ClinPred		0.90	D
GERP RS		2.9
PromoterAI		-0.050	Neutral
Varity_R		0.90
gMVP		0.68
Mutation Taster		=53/47	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: rs753686812; hg19: chr10-134000599;