rs1273198624

Variant names:

• chrX-140503818-C-G
• rs1273198624
• NM_005634.3:c.1243G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-140503818-C-G
• chrX-140503818-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005634.3(SOX3):​c.1243G>C​(p.Ala415Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 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: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: SOX3 NM_005634.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3421936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX3	NM_005634.3	c.1243G>C	p.Ala415Pro	missense_variant	Exon 1 of 1	ENST00000370536.5	NP_005625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX3	ENST00000370536.5	c.1243G>C	p.Ala415Pro	missense_variant	Exon 1 of 1	6	NM_005634.3	ENSP00000359567.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000801 AC: 1 AN: 124867 Hom.: 0 AF XY: 0.0000255 AC XY: 1 AN XY: 39249

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000439

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 Data not reliable, filtered out with message: AS_VQSR AF: 9.40e-7 AC: 1 AN: 1064236 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 1 AN XY: 345280

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000311

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	0.94	L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.33
Sift	Benign	0.099	T
Sift4G	Benign	0.22	T
Polyphen		0.96	P
Vest4		0.31
MutPred		0.18		Gain of relative solvent accessibility (P = 0.005);
MVP		0.36
ClinPred		0.41	T
GERP RS		2.6
Varity_R		0.35
gMVP		0.64

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

Other links and lift over

dbSNP: rs1273198624; hg19: chrX-139585983;