NM_003026.5:c.*927T>G

Variant names:

• chr9-17796670-T-G
• rs1049430
• NM_003026.5:c.*927T>G

Variant summary

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

The NM_003026.5(SH3GL2):​c.*927T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,522 control chromosomes in the GnomAD database, including 29,764 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 0.62 (29698 hom., cov: 33)
  • Exomes 𝑓: 0.58 (66 hom.)
• Consequence: SH3GL2 NM_003026.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 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.*927T>G		3_prime_UTR	Exon 9 of 9	NP_003017.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL2	ENST00000380607.5	TSL:1 MANE Select	c.*927T>G		3_prime_UTR	Exon 9 of 9	ENSP00000369981.4

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94018 AN: 151976 Hom.: 29670 Cov.: 33

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.593

GnomAD4 exome AF: 0.579 AC: 248 AN: 428 Hom.: 66 Cov.: 0 AF XY: 0.576 AC XY: 144 AN XY: 250

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.579 AC: 242 AN: 418

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.833 AC: 5 AN: 6

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.619 AC: 94107 AN: 152094 Hom.: 29698 Cov.: 33 AF XY: 0.619 AC XY: 46058 AN XY: 74372

African (AFR) AF: 0.713 AC: 29568 AN: 41498

American (AMR) AF: 0.473 AC: 7221 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1897 AN: 3466

East Asian (EAS) AF: 0.876 AC: 4542 AN: 5184

South Asian (SAS) AF: 0.575 AC: 2769 AN: 4816

European-Finnish (FIN) AF: 0.609 AC: 6438 AN: 10580

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39785 AN: 67958

Other (OTH) AF: 0.599 AC: 1262 AN: 2108

Alfa AF: 0.585 Hom.: 34910

Bravo AF: 0.615

Asia WGS AF: 0.713 AC: 2481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		2.0
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: rs1049430; hg19: chr9-17796668;