rs3104

Positions:

• chr14-69769024-G-A

Variant summary

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

The NM_001320214.2(SRSF5):​c.296+128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,279,584 control chromosomes in the GnomAD database, including 56,096 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 0.37 (12289 hom., cov: 33)
  • Exomes 𝑓: 0.27 (43807 hom.)
• Consequence: SRSF5 NM_001320214.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

Genes affected

SRSF5 (HGNC:10787): (serine and arginine rich splicing factor 5) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRSF5	NM_001320214.2	c.296+128G>A		intron_variant		ENST00000557154.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRSF5	ENST00000557154.6	c.296+128G>A		intron_variant		2	NM_001320214.2	P1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55782 AN: 152014 Hom.: 12237 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.266 AC: 300448 AN: 1127452 Hom.: 43807 Cov.: 15 AF XY: 0.262 AC XY: 149754 AN XY: 571396

Gnomad4 AFR exome AF: 0.612

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.367 AC: 55902 AN: 152132 Hom.: 12289 Cov.: 33 AF XY: 0.364 AC XY: 27063 AN XY: 74378

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.355

Alfa AF: 0.290 Hom.: 7627

Bravo AF: 0.384

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.070
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3104; hg19: chr14-70235741; COSMIC: COSV67936553; COSMIC: COSV67936553;