chr19-15109916-C-A

Variant names:

• chr19-15109916-C-A
• rs1343304480
• NM_033025.6:c.643C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033025.6(SYDE1):​c.643C>A​(p.Pro215Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,309,660 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SYDE1 NM_033025.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.270
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054199755).

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.643C>A	p.Pro215Thr	missense	Exon 3 of 8	NP_149014.3
	SYDE1	NM_001300910.2		c.442C>A	p.Pro148Thr	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.643C>A	p.Pro215Thr	missense	Exon 3 of 8	ENSP00000341489.1	Q6ZW31-1
	SYDE1	ENST00000600440.5	TSL:1	c.442C>A	p.Pro148Thr	missense	Exon 3 of 8	ENSP00000470733.1	Q6ZW31-2
	SYDE1	ENST00000863344.1		c.643C>A	p.Pro215Thr	missense	Exon 3 of 8	ENSP00000533403.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1309660 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 640682

African (AFR) AF: 0.00 AC: 0 AN: 26384

American (AMR) AF: 0.00 AC: 0 AN: 24526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21228

East Asian (EAS) AF: 0.00 AC: 0 AN: 32384

South Asian (SAS) AF: 0.00 AC: 0 AN: 69660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4032

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1045350

Other (OTH) AF: 0.00 AC: 0 AN: 54328

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.073
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.1
DANN	Benign	0.15
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.27
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.052
Sift	Benign	0.56	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.13		Gain of phosphorylation at P215 (P = 0.0229)
MVP		0.068
MPC		0.43
ClinPred		0.038	T
GERP RS		2.9
Varity_R		0.056
gMVP		0.29
Mutation Taster		=286/14	polymorphism

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

Other links and lift over

dbSNP: rs1343304480; hg19: chr19-15220727;