3-8985785-G-T

Variant names:

• chr3-8985785-G-T
• rs774571658
• NM_014850.4:c.3034C>A

Variant summary

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

The NM_014850.4(SRGAP3):​c.3034C>A​(p.Pro1012Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,448,172 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SRGAP3 NM_014850.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.13

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 rank	MANE	Protein	UniProt
SRGAP3	NM_014850.4	c.3034C>A	p.Pro1012Thr	missense_variant	Exon 22 of 22	ENST00000383836.8	NP_055665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRGAP3	ENST00000383836.8	c.3034C>A	p.Pro1012Thr	missense_variant	Exon 22 of 22	1	NM_014850.4	ENSP00000373347.3
SRGAP3	ENST00000360413.7	c.2962C>A	p.Pro988Thr	missense_variant	Exon 22 of 22	1		ENSP00000353587.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1448172 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720894

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;.
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.96	D;D
Vest4		0.64
MutPred		0.24		Gain of glycosylation at S1011 (P = 0.106);.;
MVP		0.043
MPC		1.6
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.42
gMVP		0.66

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: rs774571658; hg19: chr3-9027469;