chr1-23974359-T-C

Position:

• chr1-23974359-T-C

Variant summary

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

The NM_054016.4(SRSF10):​c.274+615A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,040 control chromosomes in the GnomAD database, including 11,218 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 0.35 (11218 hom., cov: 31)
• Consequence: SRSF10 NM_054016.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

Genes affected

SRSF10 (HGNC:16713): (serine and arginine rich splicing factor 10) This gene product is a member of the serine-arginine (SR) family of proteins, which are involved in constitutive and regulated RNA splicing. Members of this family are characterized by N-terminal RNP1 and RNP2 motifs, which are required for binding to RNA, and multiple C-terminal SR/RS repeats, which are important in mediating association with other cellular proteins. This protein interacts with the oncoprotein TLS, and abrogates the influence of TLS on adenovirus E1A pre-mRNA splicing. This gene has pseudogenes on chromosomes 4, 9, 14, 18, and 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRSF10	NM_054016.4	c.274+615A>G		intron_variant		ENST00000492112.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRSF10	ENST00000492112.3	c.274+615A>G		intron_variant		1	NM_054016.4	P4

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53023 AN: 151922 Hom.: 11212 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.349 AC: 53040 AN: 152040 Hom.: 11218 Cov.: 31 AF XY: 0.347 AC XY: 25774 AN XY: 74308

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.361

Alfa AF: 0.426 Hom.: 10542

Bravo AF: 0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.56

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: rs6667686; hg19: chr1-24300849;