Genetic Variant SYDE1:p.Lys153Asn (chr19-15109732-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033025.6(SYDE1):c.459A>C(p.Lys153Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,371,726 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. K153T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SYDE1
NM_033025.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.520

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11995298).

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.459A>C	p.Lys153Asn	missense	Exon 3 of 8	NP_149014.3
	SYDE1	NM_001300910.2		c.258A>C	p.Lys86Asn	missense	Exon 3 of 8	NP_001287839.1	Q6ZW31-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYDE1	ENST00000342784.7	TSL:2 MANE Select	c.459A>C	p.Lys153Asn	missense	Exon 3 of 8	ENSP00000341489.1	Q6ZW31-1
SYDE1	ENST00000600440.5	TSL:1	c.258A>C	p.Lys86Asn	missense	Exon 3 of 8	ENSP00000470733.1	Q6ZW31-2
SYDE1	ENST00000863344.1		c.459A>C	p.Lys153Asn	missense	Exon 3 of 8	ENSP00000533403.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000711

AC:

AN:

140700

AF XY:

0.0000130

show subpopulations

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:

0.0000175

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000102

AC:

AN:

1371726

Hom.:

Cov.:

AF XY:

0.00000741

AC XY:

AN XY:

674474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30514

American (AMR)

AF:

0.00

AC:

AN:

35096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23944

East Asian (EAS)

AF:

0.00

AC:

AN:

35454

South Asian (SAS)

AF:

0.00

AC:

AN:

77230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40820

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4800

European-Non Finnish (NFE)

AF:

0.0000131

AC:

AN:

1067190

Other (OTH)

AF:

0.00

AC:

AN:

56678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0043

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.74

M_CAP

Benign

0.013

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

0.52

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.0

REVEL

Benign

0.039

Sift

Uncertain

0.011

Sift4G

Benign

0.13

Polyphen

0.99

Vest4

0.17

MutPred

0.26

Loss of methylation at K153 (P = 0.0015)

MVP

0.14

MPC

0.53

ClinPred

0.18

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.14

gMVP

0.25

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over