chrX-140503972-GGCTGCGGCCGCA-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_005634.3(SOX3):​c.1077_1088del​(p.Ala361_Ala364del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,048,582 control chromosomes in the GnomAD database, including 1 homozygotes. There are 30 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (β˜…).

Frequency

Genomes: 𝑓 0.000064 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.00013 ( 1 hom. 28 hem. )

Consequence

SOX3
NM_005634.3 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.44
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 -7 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_005634.3
BP6
Variant X-140503972-GGCTGCGGCCGCA-G is Benign according to our data. Variant chrX-140503972-GGCTGCGGCCGCA-G is described in ClinVar as [Likely_benign]. Clinvar id is 2661539.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SOX3NM_005634.3 linkuse as main transcriptc.1077_1088del p.Ala361_Ala364del inframe_deletion 1/1 ENST00000370536.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SOX3ENST00000370536.5 linkuse as main transcriptc.1077_1088del p.Ala361_Ala364del inframe_deletion 1/1 NM_005634.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000640
AC:
7
AN:
109296
Hom.:
0
Cov.:
23
AF XY:
0.0000618
AC XY:
2
AN XY:
32374
show subpopulations
Gnomad AFR
AF:
0.0000331
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000948
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:
0.0000961
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000803
AC:
4
AN:
49817
Hom.:
0
AF XY:
0.0000821
AC XY:
1
AN XY:
12185
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000154
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000120
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000128
AC:
120
AN:
939286
Hom.:
1
AF XY:
0.0000972
AC XY:
28
AN XY:
288012
show subpopulations
Gnomad4 AFR exome
AF:
0.0000487
Gnomad4 AMR exome
AF:
0.0000687
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000435
Gnomad4 SAS exome
AF:
0.000125
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000135
Gnomad4 OTH exome
AF:
0.000231
GnomAD4 genome
AF:
0.0000640
AC:
7
AN:
109296
Hom.:
0
Cov.:
23
AF XY:
0.0000618
AC XY:
2
AN XY:
32374
show subpopulations
Gnomad4 AFR
AF:
0.0000331
Gnomad4 AMR
AF:
0.0000948
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000961
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000604

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 testingCeGaT Center for Human Genetics TuebingenOct 01, 2023SOX3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs756883263; hg19: chrX-139586137; API