3-8990645-C-T

Position:

• chr3-8990645-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014850.4(SRGAP3):​c.2753G>A​(p.Gly918Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SRGAP3 NM_014850.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.19

Genes affected

SRGAP3 (HGNC:19744): (SLIT-ROBO Rho GTPase activating protein 3) Predicted to enable GTPase activator activity. Predicted to be involved in negative regulation of cell migration. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP3	NM_014850.4	c.2753G>A	p.Gly918Glu	missense_variant	21/22	ENST00000383836.8	NP_055665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGAP3	ENST00000383836.8	c.2753G>A	p.Gly918Glu	missense_variant	21/22	1	NM_014850.4	ENSP00000373347.3
SRGAP3	ENST00000360413.7	c.2681G>A	p.Gly894Glu	missense_variant	21/22	1		ENSP00000353587.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.2753G>A (p.G918E) alteration is located in exon 21 (coding exon 21) of the SRGAP3 gene. This alteration results from a G to A substitution at nucleotide position 2753, causing the glycine (G) at amino acid position 918 to be replaced by a glutamic acid (E). 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	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.26	T;T
Polyphen		1.0	D;D
Vest4		0.74
MutPred		0.15		Loss of MoRF binding (P = 0.0431);.;
MVP		0.23
MPC		0.95
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.38
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-9032329;