19-15109976-T-C

Variant names:

• chr19-15109976-T-C
• NM_033025.6:c.703T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_033025.6(SYDE1):​c.703T>C​(p.Ser235Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000675 in 1,333,630 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: 0.0000067 (0 hom.)
• Consequence: SYDE1 NM_033025.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.14

Genes affected

SYDE1 (HGNC:25824): (synapse defective Rho GTPase homolog 1) The protein encoded by this gene is a Rho GTPase-activating protein highly expressed in placenta. The encoded protein is involved in cytoskeletal remodeling and trophoblast cell migration. Decreased expression of this gene has been associated with intrauterine growth restriction (IUGR). [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity SYDE1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.408535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYDE1	NM_033025.6	c.703T>C	p.Ser235Pro	missense_variant	Exon 3 of 8	ENST00000342784.7	NP_149014.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYDE1	ENST00000342784.7	c.703T>C	p.Ser235Pro	missense_variant	Exon 3 of 8	2	NM_033025.6	ENSP00000341489.1
SYDE1	ENST00000600440.5	c.502T>C	p.Ser168Pro	missense_variant	Exon 3 of 8	1		ENSP00000470733.1
SYDE1	ENST00000600252	c.-499T>C		5_prime_UTR_variant	Exon 1 of 5	2		ENSP00000469489.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000675 AC: 9 AN: 1333630 Hom.: 0 Cov.: 32 AF XY: 0.00000763 AC XY: 5 AN XY: 655526

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: 0.0000137

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000756

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.703T>C (p.S235P) alteration is located in exon 3 (coding exon 3) of the SYDE1 gene. This alteration results from a T to C substitution at nucleotide position 703, causing the serine (S) at amino acid position 235 to be replaced by a proline (P). 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	Pathogenic	0.71
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.0	D;.
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D;.
Sift4G	Benign	0.086	T;D
Polyphen		1.0	D;D
Vest4		0.52
MutPred		0.43		Loss of phosphorylation at S235 (P = 0.0028);.;
MVP		0.28
MPC		1.4
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.64
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-15220787;