19-15109991-G-T

Variant names:

• chr19-15109991-G-T
• rs920926461
• NM_033025.6:c.718G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033025.6(SYDE1):​c.718G>T​(p.Ala240Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000412 in 1,493,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (0 hom.)
• Consequence: SYDE1 NM_033025.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.116
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.054819286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033025.6. 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
	SYDE1	NM_033025.6	MANE Select	c.718G>T	p.Ala240Ser	missense	Exon 3 of 8	NP_149014.3
	SYDE1	NM_001300910.2		c.517G>T	p.Ala173Ser	missense	Exon 3 of 8	NP_001287839.1	Q6ZW31-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYDE1	ENST00000342784.7	TSL:2 MANE Select	c.718G>T	p.Ala240Ser	missense	Exon 3 of 8	ENSP00000341489.1	Q6ZW31-1
	SYDE1	ENST00000600440.5	TSL:1	c.517G>T	p.Ala173Ser	missense	Exon 3 of 8	ENSP00000470733.1	Q6ZW31-2
	SYDE1	ENST00000863344.1		c.718G>T	p.Ala240Ser	missense	Exon 3 of 8	ENSP00000533403.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152122 Hom.: 0 Cov.: 32

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: 0.000280

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000874 AC: 8 AN: 91550 AF XY: 0.0000781

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000233

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000442 AC: 593 AN: 1341358 Hom.: 0 Cov.: 32 AF XY: 0.000441 AC XY: 291 AN XY: 660166

African (AFR) AF: 0.0000731 AC: 2 AN: 27358

American (AMR) AF: 0.00 AC: 0 AN: 29532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22830

East Asian (EAS) AF: 0.00 AC: 0 AN: 32514

South Asian (SAS) AF: 0.00 AC: 0 AN: 74410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4402

European-Non Finnish (NFE) AF: 0.000513 AC: 545 AN: 1061768

Other (OTH) AF: 0.000824 AC: 46 AN: 55834

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74314

African (AFR) AF: 0.0000724 AC: 3 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000280 AC: 19 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000873 Hom.: 0

Bravo AF: 0.000196

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	0.083
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.4
DANN	Benign	0.88
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.12
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.011
Sift	Benign	0.15	T
Sift4G	Benign	0.30	T
Polyphen		0.19	B
Vest4		0.075
MutPred		0.32		Gain of glycosylation at A240 (P = 4e-04)
MVP		0.20
MPC		0.38
ClinPred		0.046	T
GERP RS		-0.35
Varity_R		0.085
gMVP		0.37
Mutation Taster		=97/3	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: rs920926461; hg19: chr19-15220802;