rs61747989

Variant names:

• chr3-8985783-G-A
• rs61747989
• NM_014850.4:c.3036C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-8985783-G-A
• chr3-8985783-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014850.4(SRGAP3):​c.3036C>T​(p.Pro1012Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,600,284 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0080 (15 hom., cov: 31)
  • Exomes 𝑓: 0.00085 (14 hom.)
• Consequence: SRGAP3 NM_014850.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.949
• Publications: 0 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-8985783-G-A is Benign according to our data. Variant chr3-8985783-G-A is described in ClinVar as Benign. ClinVar VariationId is 782421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.949 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00798 (1214/152194) while in subpopulation AFR AF = 0.027 (1122/41532). AF 95% confidence interval is 0.0257. There are 15 homozygotes in GnomAd4. There are 561 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1214 AD gene.

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.3036C>T	p.Pro1012Pro	synonymous	Exon 22 of 22	NP_055665.1	O43295-1
	SRGAP3	NM_001033117.3		c.2964C>T	p.Pro988Pro	synonymous	Exon 22 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.3036C>T	p.Pro1012Pro	synonymous	Exon 22 of 22	ENSP00000373347.3	O43295-1
	SRGAP3	ENST00000360413.7	TSL:1	c.2964C>T	p.Pro988Pro	synonymous	Exon 22 of 22	ENSP00000353587.3	O43295-2

Frequencies

GnomAD3 genomes AF: 0.00797 AC: 1212 AN: 152078 Hom.: 15 Cov.: 31

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00214 AC: 509 AN: 237400 AF XY: 0.00153

Gnomad AFR exome AF: 0.0283

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000456

Gnomad OTH exome AF: 0.000999

GnomAD4 exome AF: 0.000849 AC: 1229 AN: 1448090 Hom.: 14 Cov.: 31 AF XY: 0.000766 AC XY: 552 AN XY: 720846

African (AFR) AF: 0.0285 AC: 953 AN: 33474

American (AMR) AF: 0.00168 AC: 75 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40022

Middle Eastern (MID) AF: 0.00229 AC: 13 AN: 5680

European-Non Finnish (NFE) AF: 0.0000387 AC: 43 AN: 1111854

Other (OTH) AF: 0.00216 AC: 130 AN: 60284

GnomAD4 genome AF: 0.00798 AC: 1214 AN: 152194 Hom.: 15 Cov.: 31 AF XY: 0.00754 AC XY: 561 AN XY: 74396

African (AFR) AF: 0.0270 AC: 1122 AN: 41532

American (AMR) AF: 0.00425 AC: 65 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68002

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00296 Hom.: 5

Bravo AF: 0.00925

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	SRGAP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	4.2
DANN	Benign	0.79
PhyloP100		-0.95
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs61747989; hg19: chr3-9027467;