Y-2787279-AT-A

Variant names:

• chrY-2787279-AT-A
• rs606231179
• NM_003140.3:c.324delA

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.324delA​(p.Phe109SerfsTer72) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 0)
• Consequence: SRY NM_003140.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.245
• 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: 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 9 pathogenic variants in the truncated region.
• PP5: Variant Y-2787279-AT-A is Pathogenic according to our data. Variant chrY-2787279-AT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 9743.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRY	NM_003140.3	MANE Select	c.324delA	p.Phe109SerfsTer72	frameshift	Exon 1 of 1	NP_003131.1	A7WPU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRY	ENST00000383070.2	TSL:6 MANE Select	c.324delA	p.Phe109SerfsTer72	frameshift	Exon 1 of 1	ENSP00000372547.1	Q05066
	XGY2	ENST00000679825.1		n.392delT		non_coding_transcript_exon	Exon 4 of 4
	XGY2	ENST00000679518.1		n.106+12541delT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 13

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	46,XY sex reversal 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.24
Mutation Taster		=6/194	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs606231179; hg19: chrY-2655320;