10-132198927-T-C

Position:

• chr10-132198927-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006426.3(DPYSL4):​c.767T>C​(p.Met256Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: DPYSL4 NM_006426.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.94

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYSL4	NM_006426.3	c.767T>C	p.Met256Thr	missense_variant	8/14	ENST00000338492.9	NP_006417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL4	ENST00000338492.9	c.767T>C	p.Met256Thr	missense_variant	8/14	1	NM_006426.3	ENSP00000339850.3
DPYSL4	ENST00000368627.1	c.467T>C	p.Met156Thr	missense_variant	5/10	5		ENSP00000357616.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

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

Jul 06, 2024

The c.767T>C (p.M256T) alteration is located in exon 8 (coding exon 8) of the DPYSL4 gene. This alteration results from a T to C substitution at nucleotide position 767, causing the methionine (M) at amino acid position 256 to be replaced by a threonine (T). 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	0.16
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.64	D;T
Eigen	Benign	0.057
Eigen_PC	Benign	0.0095
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	-0.045	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Pathogenic	0.75
Sift	Benign	0.33	T;T
Sift4G	Benign	0.91	T;T
Polyphen		0.98	D;.
Vest4		0.96
MutPred		0.73		Loss of catalytic residue at V252 (P = 0.0229);.;
MVP		0.95
MPC		1.0
ClinPred		0.96	D
GERP RS		2.8
Varity_R		0.76
gMVP		0.96

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: rs1158254873; hg19: chr10-134012431;