dbSNP rs11575897: SRY:p.Ser155Ser (chrY-2787139-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003140.3(SRY):c.465C>T(p.Ser155Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., 59 hem., cov: 0)

Exomes 𝑓: 0.0056 ( 0 hom. 2036 hem. )

Consequence

SRY
NM_003140.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.93

Publications

12 publications found

Variant links:

Genes affected

SRY (HGNC:11311): (sex determining region Y) This intronless gene encodes a transcription factor that is a member of the high mobility group (HMG)-box family of DNA-binding proteins. This protein is the testis-determining factor (TDF), which initiates male sex determination. Mutations in this gene give rise to XY females with gonadal dysgenesis (Swyer syndrome); translocation of part of the Y chromosome containing this gene to the X chromosome causes XX male syndrome. [provided by RefSeq, Jul 2008]

SRY links:

XGY2 (HGNC:34022): (XG Y-linked 2 (pseudogene))

XGY2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant Y-2787139-G-A is Benign according to our data. Variant chrY-2787139-G-A is described in ClinVar as [Benign]. Clinvar id is 703672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.93 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRY	NM_003140.3 link	c.465C>T	p.Ser155Ser	synonymous_variant	Exon 1 of 1	ENST00000383070.2	NP_003131.1	Q05066A7WPU8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRY	ENST00000383070.2 link	c.465C>T	p.Ser155Ser	synonymous_variant	Exon 1 of 1	6	NM_003140.3	ENSP00000372547.1		Q05066

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

AN:

33241

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0470

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00521

AC:

321

AN:

61669

AF XY:

0.00521

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0757

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.00563

AC:

2036

AN:

361447

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

2036

AN XY:

361447

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7057

American (AMR)

AF:

0.00

AC:

AN:

9312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6712

East Asian (EAS)

AF:

0.214

AC:

2022

AN:

9451

South Asian (SAS)

AF:

0.00

AC:

AN:

31701

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12774

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1627

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

268613

Other (OTH)

AF:

0.000986

AC:

AN:

14200

GnomAD4 genome

AF:

0.00177

AC:

AN:

33305

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

AN XY:

33305

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8524

American (AMR)

AF:

0.00

AC:

AN:

3642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

769

East Asian (EAS)

AF:

0.0470

AC:

AN:

1255

South Asian (SAS)

AF:

0.00

AC:

AN:

1469

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3353

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

13543

Other (OTH)

AF:

0.00

AC:

AN:

460

Alfa

AF:

0.0317

Hom.:

980

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 20, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

46,XY sex reversal 1

Benign:1

Nov 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.1

(source)

DANN

Benign

0.82

PhyloP100

2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs11575897

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