rs13047599

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138927.4(SON):c.4723C>T(p.Arg1575Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,613,556 control chromosomes in the GnomAD database, including 378,461 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1575H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.70 ( 37793 hom., cov: 32)

Exomes 𝑓: 0.68 ( 340668 hom. )

Consequence

SON
NM_138927.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0430

Publications

47 publications found

Variant links:

Genes affected

SON (HGNC:11183): (SON DNA and RNA binding protein) This gene encodes a protein that contains multiple simple repeats. The encoded protein binds RNA and promotes pre-mRNA splicing, particularly of transcripts with poor splice sites. The protein also recognizes a specific DNA sequence found in the human hepatitis B virus (HBV) and represses HBV core promoter activity. There is a pseudogene for this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

SON Gene-Disease associations (from GenCC):

ZTTK syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

SON links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.871352E-7).

BP6

Variant 21-33553954-C-T is Benign according to our data. Variant chr21-33553954-C-T is described in ClinVar as [Benign]. Clinvar id is 1170805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SON	NM_138927.4 link	c.4723C>T	p.Arg1575Cys	missense_variant	Exon 3 of 12	ENST00000356577.10	NP_620305.3	P18583-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SON	ENST00000356577.10 link	c.4723C>T	p.Arg1575Cys	missense_variant	Exon 3 of 12	1	NM_138927.4	ENSP00000348984.4		P18583-1

Frequencies

GnomAD3 genomes

AF:

0.704

AC:

107012

AN:

151930

Hom.:

37772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.767

Gnomad AMI

AF:

0.683

Gnomad AMR

AF:

0.707

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.731

Gnomad SAS

AF:

0.655

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.676

GnomAD2 exomes

AF:

0.678

AC:

170442

AN:

251266

AF XY:

0.675

show subpopulations

Gnomad AFR exome

AF:

0.772

Gnomad AMR exome

AF:

0.669

Gnomad ASJ exome

AF:

0.590

Gnomad EAS exome

AF:

0.742

Gnomad FIN exome

AF:

0.703

Gnomad NFE exome

AF:

0.670

Gnomad OTH exome

AF:

0.673

GnomAD4 exome

AF:

0.682

AC:

996696

AN:

1461508

Hom.:

340668

Cov.:

AF XY:

0.680

AC XY:

494193

AN XY:

727086

show subpopulations

African (AFR)

AF:

0.768

AC:

25714

AN:

33474

American (AMR)

AF:

0.671

AC:

29999

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.593

AC:

15493

AN:

26132

East Asian (EAS)

AF:

0.741

AC:

29429

AN:

39692

South Asian (SAS)

AF:

0.645

AC:

55673

AN:

86256

European-Finnish (FIN)

AF:

0.696

AC:

37136

AN:

53392

Middle Eastern (MID)

AF:

0.590

AC:

3403

AN:

5768

European-Non Finnish (NFE)

AF:

0.682

AC:

758616

AN:

1111696

Other (OTH)

AF:

0.683

AC:

41233

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

17848

35696

53543

71391

89239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.704

AC:

107074

AN:

152048

Hom.:

37793

Cov.:

AF XY:

0.707

AC XY:

52514

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.767

AC:

31794

AN:

41468

American (AMR)

AF:

0.707

AC:

10792

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.582

AC:

2020

AN:

3468

East Asian (EAS)

AF:

0.731

AC:

3785

AN:

5176

South Asian (SAS)

AF:

0.653

AC:

3145

AN:

4814

European-Finnish (FIN)

AF:

0.710

AC:

7507

AN:

10574

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.674

AC:

45837

AN:

67964

Other (OTH)

AF:

0.671

AC:

1414

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1606

3212

4817

6423

8029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.681

Hom.:

112823

Bravo

AF:

0.706

TwinsUK

AF:

0.689

AC:

2556

ALSPAC

AF:

0.676

AC:

2606

ESP6500AA

AF:

0.766

AC:

3377

ESP6500EA

AF:

0.673

AC:

5791

ExAC

AF:

0.678

AC:

82291

Asia WGS

AF:

0.691

AC:

2404

AN:

3478

EpiCase

AF:

0.665

EpiControl

AF:

0.665

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 10, 2022

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

ZTTK syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.4

(source)

DANN

Benign

0.040

DEOGEN2

Benign

0.015

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.16

T;T;T

MetaRNN

Benign

9.9e-7

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.7

N;N;N

PhyloP100

-0.043

PrimateAI

Benign

0.38

PROVEAN

Benign

2.0

N;N;N

REVEL

Benign

0.029

Sift

Benign

0.66

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.049

MPC

0.12

ClinPred

0.00019

GERP RS

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.050

gMVP

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs13047599

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over