3-8985742-C-T

Position:

• chr3-8985742-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014850.4(SRGAP3):​c.3077G>A​(p.Arg1026His) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,802 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SRGAP3 NM_014850.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.03

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29521817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRGAP3	NM_014850.4	c.3077G>A	p.Arg1026His	missense_variant	22/22	ENST00000383836.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGAP3	ENST00000383836.8	c.3077G>A	p.Arg1026His	missense_variant	22/22	1	NM_014850.4	P1
SRGAP3	ENST00000360413.7	c.3005G>A	p.Arg1002His	missense_variant	22/22	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446802 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720162

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Dec 04, 2019

This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.94	N;N
REVEL	Benign	0.25
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.050	T;D
Polyphen		1.0	D;D
Vest4		0.48
MutPred		0.13		Loss of MoRF binding (P = 0.0237);.;
MVP		0.11
MPC		1.3
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.22
gMVP		0.30

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: rs1488419249; hg19: chr3-9027426;