dbSNP rs300703: SH3YL1:c.292-5144G>A (chr2-239416-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015677.4(SH3YL1):c.292-5144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,264 control chromosomes in the GnomAD database, including 63,602 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 0.91 ( 63596 hom., cov: 32)

Exomes 𝑓: 0.93 ( 6 hom. )

Consequence

SH3YL1
NM_015677.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.98

Publications

6 publications found

Variant links:

Genes affected

SH3YL1 (HGNC:29546): (SH3 and SYLF domain containing 1) Enables phosphatase binding activity and phosphatidylinositol binding activity. Predicted to act upstream of or within phosphatidylinositol biosynthetic process and regulation of ruffle assembly. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

SH3YL1 links:

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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=-1.08).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SH3YL1	NM_015677.4	MANE Select	c.292-5144G>A	intron	N/A	NP_056492.2
SH3YL1	NM_001159597.3		c.292-5144G>A	intron	N/A	NP_001153069.1
SH3YL1	NM_001282687.2		c.3+3382G>A	intron	N/A	NP_001269616.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SH3YL1	ENST00000356150.10	TSL:1 MANE Select	c.292-5144G>A	intron	N/A	ENSP00000348471.5
SH3YL1	ENST00000403712.6	TSL:1	c.292-5144G>A	intron	N/A	ENSP00000384276.1
SH3YL1	ENST00000626873.2	TSL:5	c.3+3382G>A	intron	N/A	ENSP00000485824.1

Frequencies

GnomAD3 genomes

AF:

0.913

AC:

138906

AN:

152132

Hom.:

63540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.968

Gnomad AMI

AF:

0.825

Gnomad AMR

AF:

0.893

Gnomad ASJ

AF:

0.884

Gnomad EAS

AF:

0.897

Gnomad SAS

AF:

0.921

Gnomad FIN

AF:

0.844

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.899

Gnomad OTH

AF:

0.906

GnomAD4 exome

AF:

0.929

AC:

AN:

Hom.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.833

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.913

AC:

139019

AN:

152250

Hom.:

63596

Cov.:

AF XY:

0.910

AC XY:

67742

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.968

AC:

40200

AN:

41534

American (AMR)

AF:

0.893

AC:

13664

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.884

AC:

3068

AN:

3470

East Asian (EAS)

AF:

0.897

AC:

4653

AN:

5188

South Asian (SAS)

AF:

0.920

AC:

4440

AN:

4826

European-Finnish (FIN)

AF:

0.844

AC:

8932

AN:

10588

Middle Eastern (MID)

AF:

0.908

AC:

267

AN:

294

European-Non Finnish (NFE)

AF:

0.899

AC:

61129

AN:

68028

Other (OTH)

AF:

0.905

AC:

1914

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

618

1236

1853

2471

3089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<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:

0.914

Hom.:

22522

Bravo

AF:

0.920

Asia WGS

AF:

0.911

AC:

3164

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.34

(source)

DANN

Benign

0.66

PhyloP100

-5.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over