rs754547731

Variant names:

• chr3-8990735-C-G
• rs754547731
• NM_014850.4:c.2663G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-8990735-C-G
• chr3-8990735-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014850.4(SRGAP3):​c.2663G>C​(p.Arg888Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R888Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SRGAP3 NM_014850.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39734364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014850.4. 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
	SRGAP3	NM_014850.4	MANE Select	c.2663G>C	p.Arg888Pro	missense	Exon 21 of 22	NP_055665.1	O43295-1
	SRGAP3	NM_001033117.3		c.2591G>C	p.Arg864Pro	missense	Exon 21 of 22	NP_001028289.1	O43295-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGAP3	ENST00000383836.8	TSL:1 MANE Select	c.2663G>C	p.Arg888Pro	missense	Exon 21 of 22	ENSP00000373347.3	O43295-1
	SRGAP3	ENST00000360413.7	TSL:1	c.2591G>C	p.Arg864Pro	missense	Exon 21 of 22	ENSP00000353587.3	O43295-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457708 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724896

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 85702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5362

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110926

Other (OTH) AF: 0.00 AC: 0 AN: 60060

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.0084	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.7
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.29	N
REVEL	Benign	0.24
Sift	Benign	0.30	T
Sift4G	Benign	0.28	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.23		Gain of glycosylation at R888 (P = 0.0158)
MVP		0.082
MPC		1.9
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.36
gMVP		0.58
Mutation Taster		=49/51	disease causing

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: rs754547731; hg19: chr3-9032419;