Genetic Variant SH3GL2:c.*927T>G (chr9-17796670-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Publications

7 publications found

Variant links:

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]

SH3GL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SH3GL2	NM_003026.5 link	c.*927T>G	3_prime_UTR_variant	Exon 9 of 9	ENST00000380607.5	NP_003017.1	Q99962Q7Z376
SH3GL2	XM_011518005.4 link	c.*927T>G	3_prime_UTR_variant	Exon 9 of 9		XP_011516307.1
SH3GL2	XM_047423730.1 link	c.*927T>G	3_prime_UTR_variant	Exon 9 of 9		XP_047279686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3GL2	ENST00000380607.5 link	c.*927T>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_003026.5	ENSP00000369981.4		Q99962

Frequencies

GnomAD3 genomes

AF:

0.619

AC:

94018

AN:

151976

Hom.:

29670

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.576

AC XY:

144

AN XY:

250

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.579

AC:

242

AN:

418

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.833

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.619

AC:

94107

AN:

152094

Hom.:

29698

Cov.:

AF XY:

0.619

AC XY:

46058

AN XY:

74372

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1819

3638

5457

7276

9095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over