Genetic Variant SYDE1:p.Arg186Trp (chr19-15109829-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033025.6(SYDE1):c.556C>T(p.Arg186Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000652 in 1,533,386 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R186Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

SYDE1
NM_033025.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0990

Variant links:

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]

SYDE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21870089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYDE1	NM_033025.6 link	c.556C>T	p.Arg186Trp	missense_variant	Exon 3 of 8	ENST00000342784.7	NP_149014.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYDE1	ENST00000342784.7 link	c.556C>T	p.Arg186Trp	missense_variant	Exon 3 of 8	2	NM_033025.6	ENSP00000341489.1	Q6ZW31-1
SYDE1	ENST00000600440.5 link	c.355C>T	p.Arg119Trp	missense_variant	Exon 3 of 8	1		ENSP00000470733.1	Q6ZW31-2
SYDE1	ENST00000600252 link	c.-646C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	2		ENSP00000469489.1	M0QXZ8
SYDE1	ENST00000600252 link	c.-646C>T		5_prime_UTR_variant	Exon 1 of 5	2		ENSP00000469489.1	M0QXZ8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000507

AC:

AN:

1381250

Hom.:

Cov.:

AF XY:

0.00000587

AC XY:

AN XY:

681392

show subpopulations

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:

0.00000650

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000357

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000198

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.556C>T (p.R186W) alteration is located in exon 3 (coding exon 3) of the SYDE1 gene. This alteration results from a C to T substitution at nucleotide position 556, causing the arginine (R) at amino acid position 186 to be replaced by a tryptophan (W). 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

0.25

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.88

D;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;.

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.8

D;.

REVEL

Benign

0.11

Sift

Benign

0.034

D;.

Sift4G

Uncertain

0.013

D;D

Polyphen

0.99

D;D

Vest4

0.23

MutPred

0.32

Loss of methylation at R186 (P = 0.0145);.;

MVP

0.19

MPC

1.1

ClinPred

0.81

GERP RS

1.2

Varity_R

0.072

gMVP

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over