Variant chrY-2787334-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PP3_StrongPP5

The NM_003140.3(SRY):c.270C>G(p.Ile90Met) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

SRY
NM_003140.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 4.20

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 made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1

In a chain Sex-determining region Y protein (size 203) in uniprot entity SRY_HUMAN there are 14 pathogenic changes around while only 0 benign (100%) in NM_003140.3

PP3

MetaRNN computational evidence supports a deleterious effect, 0.994

PP5

Variant Y-2787334-G-C is Pathogenic according to our data. Variant chrY-2787334-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 9741.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrY-2787334-G-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRY	NM_003140.3 linkuse as main transcript	c.270C>G	p.Ile90Met	missense_variant	1/1	ENST00000383070.2	NP_003131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRY	ENST00000383070.2 linkuse as main transcript	c.270C>G	p.Ile90Met	missense_variant	1/1		NM_003140.3	ENSP00000372547	P1
XGY2	ENST00000681940.1 linkuse as main transcript	n.106+12595G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000148

AC:

AN:

67342

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67342

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000317

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000550

AC:

AN:

363377

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363377

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000741

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

46,XY true hermaphroditism, SRY-related

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2003

- -

46,XY sex reversal 1

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Pathogenic

0.55

BayesDel_noAF

Pathogenic

0.65

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.90

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

1.0

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.7

MutationTaster

Benign

1.0

A;A

PROVEAN

Uncertain

-3.0

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.86

MutPred

0.97

Gain of disorder (P = 0.011);

MVP

1.0

MPC

1.1

ClinPred

0.97

GERP RS

0.64

Varity_R

0.93

gMVP

0.97

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over