rs10515752

Positions:

• chr5-157645369-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178424.2(SOX30):​c.1387+1268C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,008 control chromosomes in the GnomAD database, including 2,454 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2454 hom., cov: 32)
• Consequence: SOX30 NM_178424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

SOX30 (HGNC:30635): (SRY-box transcription factor 30) 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 acts as a transcriptional regulator when present in a complex with other proteins. It can activate p53 transcription to promote tumor cell apoptosis in lung cancer. The protein may be involved in the differentiation of developing male germ cells. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX30	NM_178424.2	c.1387+1268C>T		intron_variant		ENST00000265007.11
SOX30	NM_001308165.2	c.472+1268C>T		intron_variant
SOX30	NM_007017.3	c.1387+1268C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX30	ENST00000265007.11	c.1387+1268C>T		intron_variant		1	NM_178424.2	P2
SOX30	ENST00000311371.9	c.1387+1268C>T		intron_variant		1		A2
SOX30	ENST00000519442.1	c.472+1268C>T		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25341 AN: 151890 Hom.: 2453 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0684

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.167 AC: 25361 AN: 152008 Hom.: 2454 Cov.: 32 AF XY: 0.166 AC XY: 12310 AN XY: 74290

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.189

Alfa AF: 0.149 Hom.: 223

Bravo AF: 0.173

Asia WGS AF: 0.0940 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.50
DANN	Benign	0.48

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: rs10515752; hg19: chr5-157072377;