Genetic Variant NM_003026.5: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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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