chrY-2787330-T-A

Variant names:

• chrY-2787330-T-A
• rs104894970
• NM_003140.3:c.274A>T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_Strong PP5

The NM_003140.3(SRY):​c.274A>T​(p.Lys92*) variant causes a stop gained 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: 1)
• Consequence: SRY NM_003140.3 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.15
• Publications: 1 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: Uncertain_significance. The variant received 5 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 17 pathogenic variants in the truncated region.
• PP5: Variant Y-2787330-T-A is Pathogenic according to our data. Variant chrY-2787330-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 9749.Status of the report is no_assertion_criteria_provided, 0 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.274A>T	p.Lys92*	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.274A>T	p.Lys92*	stop_gained	Exon 1 of 1	ENSP00000372547.1
	XGY2	ENST00000679825.1		n.442T>A		non_coding_transcript_exon	Exon 4 of 4
	XGY2	ENST00000679518.1		n.106+12591T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 1

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

46,XY sex reversal 1 Pathogenic:1

Jul 01, 1992

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.70	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	33
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.55	D
PhyloP100		4.1
Vest4		0.72
GERP RS		0.64
PromoterAI		0.0068	Neutral
Mutation Taster		=0/200	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs104894970; hg19: chrY-2655371;