chr10-132198418-C-G

Variant names:

• chr10-132198418-C-G
• rs760321119
• NM_006426.3:c.625C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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.625C>G	p.Gln209Glu	missense	Exon 7 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.625C>G	p.Gln209Glu	missense	Exon 7 of 14	ENSP00000339850.3	O14531
	DPYSL4	ENST00000905073.1		c.625C>G	p.Gln209Glu	missense	Exon 7 of 14	ENSP00000575132.1
	DPYSL4	ENST00000905072.1		c.625C>G	p.Gln209Glu	missense	Exon 7 of 14	ENSP00000575131.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 43932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25900

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.00 AC: 0 AN: 84418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109442

Other (OTH) AF: 0.00 AC: 0 AN: 60124

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.4
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
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs760321119; hg19: chr10-134011922;