Y-2787139-G-C

Position:

• chrY-2787139-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1 BP4_Moderate

The NM_003140.3(SRY):​c.465C>G​(p.Ser155Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: SRY NM_003140.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

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

Verdict is Uncertain_significance. Variant got 0 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
• BP4: Computational evidence support a benign effect (MetaRNN=0.24544457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRY	NM_003140.3	c.465C>G	p.Ser155Arg	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	c.465C>G	p.Ser155Arg	missense_variant	1/1	6	NM_003140.3	ENSP00000372547.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 6

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	11
DANN	Benign	0.56
DEOGEN2	Benign	0.14	T
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	1.0	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	-0.090	N
PROVEAN	Benign	-1.5	N
Sift	Benign	0.81	T
Sift4G	Benign	0.27	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.31		Gain of loop (P = 0.1069);
MVP		0.98
MPC		0.38
ClinPred		0.040	T
GERP RS		0.64
Varity_R		0.20
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrY-2655180;