19-15109127-G-A

Variant names:

• chr19-15109127-G-A
• rs567072793
• NM_033025.6:c.160G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_033025.6(SYDE1):​c.160G>A​(p.Gly54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000968 in 1,549,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: SYDE1 NM_033025.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.52

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086301714).
• BP6: Variant 19-15109127-G-A is Benign according to our data. Variant chr19-15109127-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2466184.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYDE1	NM_033025.6	c.160G>A	p.Gly54Arg	missense_variant	Exon 2 of 8	ENST00000342784.7	NP_149014.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYDE1	ENST00000342784.7	c.160G>A	p.Gly54Arg	missense_variant	Exon 2 of 8	2	NM_033025.6	ENSP00000341489.1
SYDE1	ENST00000600440.5	c.89-130G>A		intron_variant	Intron 1 of 7	1		ENSP00000470733.1
SYDE1	ENST00000597977.5	c.160G>A	p.Gly54Arg	missense_variant	Exon 2 of 2	2		ENSP00000473151.1
SYDE1	ENST00000600252	c.-1348G>A		5_prime_UTR_variant	Exon 1 of 5	2		ENSP00000469489.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000202 AC: 3 AN: 148160 Hom.: 0 AF XY: 0.0000126 AC XY: 1 AN XY: 79282

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000269

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000930 AC: 13 AN: 1397698 Hom.: 0 Cov.: 32 AF XY: 0.00000725 AC XY: 5 AN XY: 689472

Gnomad4 AFR exome AF: 0.0000633

Gnomad4 AMR exome AF: 0.0000281

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000559

Gnomad4 SAS exome AF: 0.0000379

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000464

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74344

Gnomad4 AFR AF: 0.0000241

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: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ExAC AF: 0.0000325 AC: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 01, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.086	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.69	N;.
REVEL	Benign	0.010
Sift	Uncertain	0.0050	D;.
Sift4G	Benign	0.59	T;T
Polyphen		0.019	B;.
Vest4		0.23
MutPred		0.21		Gain of methylation at G54 (P = 0.0183);Gain of methylation at G54 (P = 0.0183);
MVP		0.043
MPC		0.47
ClinPred		0.065	T
GERP RS		2.3
Varity_R		0.091
gMVP		0.28

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: rs567072793; hg19: chr19-15219938;