dbSNP rs3818668: SHC3:c.784-36G>C (chr9-89065616-C-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_016848.6(SHC3):c.784-36G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 1,609,956 control chromosomes in the GnomAD database, including 459,195 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 0.66 ( 35372 hom., cov: 31)

Exomes 𝑓: 0.76 ( 423823 hom. )

Consequence

SHC3
NM_016848.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.419

Publications

6 publications found

Variant links:

Genes affected

SHC3 (HGNC:18181): (SHC adaptor protein 3) Enables phosphotyrosine residue binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within glutamatergic synaptic transmission and learning or memory. Predicted to be located in cytosol. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SHC3 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC3	NM_016848.6 link	c.784-36G>C		intron_variant	Intron 5 of 11	ENST00000375835.9	NP_058544.3	Q92529-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC3	ENST00000375835.9 link	c.784-36G>C		intron_variant	Intron 5 of 11	1	NM_016848.6	ENSP00000364995.4		Q92529-1

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99606

AN:

151894

Hom.:

35361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.802

Gnomad AMR

AF:

0.754

Gnomad ASJ

AF:

0.719

Gnomad EAS

AF:

0.975

Gnomad SAS

AF:

0.848

Gnomad FIN

AF:

0.768

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.755

Gnomad OTH

AF:

0.682

GnomAD2 exomes

AF:

0.762

AC:

190547

AN:

250184

AF XY:

0.769

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.818

Gnomad ASJ exome

AF:

0.715

Gnomad EAS exome

AF:

0.982

Gnomad FIN exome

AF:

0.767

Gnomad NFE exome

AF:

0.751

Gnomad OTH exome

AF:

0.755

GnomAD4 exome

AF:

0.758

AC:

1105541

AN:

1457944

Hom.:

423823

Cov.:

AF XY:

0.761

AC XY:

552221

AN XY:

725584

show subpopulations

African (AFR)

AF:

0.339

AC:

11320

AN:

33364

American (AMR)

AF:

0.814

AC:

36385

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.716

AC:

18694

AN:

26098

East Asian (EAS)

AF:

0.971

AC:

38553

AN:

39698

South Asian (SAS)

AF:

0.835

AC:

71911

AN:

86162

European-Finnish (FIN)

AF:

0.761

AC:

40234

AN:

52858

Middle Eastern (MID)

AF:

0.704

AC:

4052

AN:

5758

European-Non Finnish (NFE)

AF:

0.757

AC:

839514

AN:

1109038

Other (OTH)

AF:

0.745

AC:

44878

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

13683

27366

41048

54731

68414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20274

40548

60822

81096

101370

<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:

0.655

AC:

99637

AN:

152012

Hom.:

35372

Cov.:

AF XY:

0.662

AC XY:

49190

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.355

AC:

14724

AN:

41448

American (AMR)

AF:

0.754

AC:

11517

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.719

AC:

2495

AN:

3468

East Asian (EAS)

AF:

0.975

AC:

5038

AN:

5166

South Asian (SAS)

AF:

0.848

AC:

4077

AN:

4808

European-Finnish (FIN)

AF:

0.768

AC:

8123

AN:

10574

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.755

AC:

51306

AN:

67956

Other (OTH)

AF:

0.685

AC:

1446

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1516

3031

4547

6062

7578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.701

Hom.:

7122

Bravo

AF:

0.640

Asia WGS

AF:

0.871

AC:

3029

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.4

(source)

DANN

Benign

0.69

PhyloP100

-0.42

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