Y-2787273-G-A

Variant names:

• chrY-2787273-G-A
• rs1556370543
• NM_003140.3:c.331C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PP5_Moderate

The NM_003140.3(SRY):​c.331C>T​(p.Gln111*) variant causes a stop gained change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: SRY NM_003140.3 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.07
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
• PP5: Variant Y-2787273-G-A is Pathogenic according to our data. Variant chrY-2787273-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 436871.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003140.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRY	NM_003140.3	MANE Select	c.331C>T	p.Gln111*	stop_gained	Exon 1 of 1	NP_003131.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRY	ENST00000383070.2	TSL:6 MANE Select	c.331C>T	p.Gln111*	stop_gained	Exon 1 of 1	ENSP00000372547.1
	XGY2	ENST00000679825.1		n.385G>A		non_coding_transcript_exon	Exon 4 of 4
	XGY2	ENST00000679518.1		n.106+12534G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

46,XX sex reversal 1;C2748896:46,XY sex reversal 1 Pathogenic:1

Nov 03, 2015

Genetic Services Laboratory, University of Chicago

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.70	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	27
DANN	Benign	0.96
FATHMM_MKL	Benign	0.37	N
PhyloP100		4.1
Vest4		0.61
GERP RS		-0.84
PromoterAI		-0.025	Neutral
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1556370543; hg19: chrY-2655314;