NM_003140.3:c.321G>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PP2PP3
The NM_003140.3(SRY):c.321G>T(p.Trp107Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )
Consequence
SRY
NM_003140.3 missense
NM_003140.3 missense
Scores
3
7
4
Clinical Significance
Conservation
PhyloP100: -0.0280
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]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM1
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 1 uncertain in NM_003140.3
PP2
Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 19 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: -0.13831 (below the threshold of 3.09). Trascript score misZ: NaN (below the threshold of 3.09). GenCC associations: The gene is linked to 46,XX sex reversal 1, 46,XY sex reversal 1, 46,XY partial gonadal dysgenesis, 46,XX ovotesticular disorder of sex development, 46,XY complete gonadal dysgenesis.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.809
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.
Ensembl Transcripts
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
0
GnomAD4 exome AF: 0.00000276 AC: 1AN: 362486Hom.: 0 Cov.: 10 AF XY: 0.00000276 AC XY: 1AN XY: 362486 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
362486
Hom.:
Cov.:
10
AF XY:
AC XY:
1
AN XY:
362486
show subpopulations
African (AFR)
AF:
AC:
0
AN:
7067
American (AMR)
AF:
AC:
1
AN:
9452
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
6727
East Asian (EAS)
AF:
AC:
0
AN:
9481
South Asian (SAS)
AF:
AC:
0
AN:
31877
European-Finnish (FIN)
AF:
AC:
0
AN:
12826
Middle Eastern (MID)
AF:
AC:
0
AN:
1627
European-Non Finnish (NFE)
AF:
AC:
0
AN:
269167
Other (OTH)
AF:
AC:
0
AN:
14262
GnomAD4 genome
GnomAD4 genome
Cov.:
0
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
46,XY sex reversal 1 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Uncertain
D
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
PhyloP100
PROVEAN
Uncertain
D
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0241)
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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