9-17608786-T-C

Variant names:

• chr9-17608786-T-C
• rs2145656
• NM_003026.5:c.45+29499T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003026.5(SH3GL2):​c.45+29499T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,168 control chromosomes in the GnomAD database, including 2,373 homozygotes. 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: 𝑓 0.17 (2373 hom., cov: 33)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.945
• Publications: 3 publications found

Genes affected

SH3GL2 (HGNC:10831): (SH3 domain containing GRB2 like 2, endophilin A1) Enables identical protein binding activity. Involved in negative regulation of blood-brain barrier permeability; negative regulation of gene expression; and negative regulation of protein phosphorylation. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000298472 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003026.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL2	NM_003026.5	MANE Select	c.45+29499T>C		intron	N/A	NP_003017.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL2	ENST00000380607.5	TSL:1 MANE Select	c.45+29499T>C		intron	N/A	ENSP00000369981.4
	SH3GL2	ENST00000467085.1	TSL:5	n.207-21568T>C		intron	N/A
	ENSG00000298472	ENST00000755729.1		n.436-45276T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25782 AN: 152050 Hom.: 2376 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.170 AC: 25795 AN: 152168 Hom.: 2373 Cov.: 33 AF XY: 0.170 AC XY: 12672 AN XY: 74398

African (AFR) AF: 0.111 AC: 4603 AN: 41534

American (AMR) AF: 0.153 AC: 2345 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3468

East Asian (EAS) AF: 0.279 AC: 1444 AN: 5170

South Asian (SAS) AF: 0.295 AC: 1420 AN: 4814

European-Finnish (FIN) AF: 0.163 AC: 1720 AN: 10584

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.193 AC: 13151 AN: 67998

Other (OTH) AF: 0.158 AC: 333 AN: 2110

Alfa AF: 0.183 Hom.: 2898

Bravo AF: 0.165

Asia WGS AF: 0.262 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.63
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism (auto)

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: rs2145656; hg19: chr9-17608784;