chrX-140503968-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005634.3(SOX3):ā€‹c.1093A>Cā€‹(p.Met365Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000807 in 1,053,436 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00046 ( 0 hom., 17 hem., cov: 23)
Exomes š‘“: 0.000037 ( 0 hom. 1 hem. )

Consequence

SOX3
NM_005634.3 missense

Scores

2
1
14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.64
Variant links:
Genes affected
SOX3 (HGNC:11199): (SRY-box transcription factor 3) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. Mutations in this gene have been associated with X-linked cognitive disability with growth hormone deficiency. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.032978266).
BP6
Variant X-140503968-T-G is Benign according to our data. Variant chrX-140503968-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 798184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Hemizygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SOX3NM_005634.3 linkuse as main transcriptc.1093A>C p.Met365Leu missense_variant 1/1 ENST00000370536.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SOX3ENST00000370536.5 linkuse as main transcriptc.1093A>C p.Met365Leu missense_variant 1/1 NM_005634.3 P1

Frequencies

GnomAD3 genomes
AF:
0.000465
AC:
50
AN:
107538
Hom.:
0
Cov.:
23
AF XY:
0.000541
AC XY:
17
AN XY:
31414
show subpopulations
Gnomad AFR
AF:
0.00162
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000192
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000329
AC:
2
AN:
60760
Hom.:
0
AF XY:
0.0000661
AC XY:
1
AN XY:
15140
show subpopulations
Gnomad AFR exome
AF:
0.000666
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000370
AC:
35
AN:
945864
Hom.:
0
Cov.:
30
AF XY:
0.00000346
AC XY:
1
AN XY:
288878
show subpopulations
Gnomad4 AFR exome
AF:
0.00149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000430
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000766
GnomAD4 genome
AF:
0.000465
AC:
50
AN:
107572
Hom.:
0
Cov.:
23
AF XY:
0.000540
AC XY:
17
AN XY:
31456
show subpopulations
Gnomad4 AFR
AF:
0.00161
Gnomad4 AMR
AF:
0.000192
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000381
Hom.:
2
Bravo
AF:
0.000450
ExAC
AF:
0.0000793
AC:
8

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeNov 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
18
DANN
Benign
0.65
DEOGEN2
Benign
0.40
T
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.35
T
M_CAP
Pathogenic
0.66
D
MetaRNN
Benign
0.033
T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
0.87
D
PrimateAI
Pathogenic
0.96
D
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.21
Sift
Benign
0.12
T
Sift4G
Benign
0.32
T
Polyphen
0.0
B
Vest4
0.24
MutPred
0.34
Loss of loop (P = 0.0374);
MVP
0.42
ClinPred
0.028
T
GERP RS
2.9
Varity_R
0.51
gMVP
0.43

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780036573; hg19: chrX-139586133; API