NM_014850.4:c.3034C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_014850.4(SRGAP3):​c.3034C>T​(p.Pro1012Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,448,172 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34148937).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRGAP3	NM_014850.4	c.3034C>T	p.Pro1012Ser	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>T	p.Pro1012Ser	missense_variant	Exon 22 of 22	1	NM_014850.4	ENSP00000373347.3
SRGAP3	ENST00000360413.7	c.2962C>T	p.Pro988Ser	missense_variant	Exon 22 of 22	1		ENSP00000353587.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1448172 Hom.: 0 Cov.: 31 AF XY: 0.00000416 AC XY: 3 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: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.0042	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.51	D;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.17
Sift	Benign	0.10	T;T
Sift4G	Uncertain	0.033	D;D
Polyphen		0.96	D;D
Vest4		0.55
MutPred		0.22		Gain of phosphorylation at P1012 (P = 0.0478);.;
MVP		0.068
MPC		1.6
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.27
gMVP		0.68

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;