6-36602589-T-C

Position:

• chr6-36602589-T-C

Variant summary

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

The ENST00000373715.11(SRSF3):​c.*600T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 217,416 control chromosomes in the GnomAD database, including 5,754 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 0.20 (3418 hom., cov: 32)
  • Exomes 𝑓: 0.25 (2336 hom.)
• Consequence: SRSF3 ENST00000373715.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

Genes affected

SRSF3 (HGNC:10785): (serine and arginine rich splicing factor 3) 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. Two transcript variants, one protein-coding and the other non-coding, have been found for this gene. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRSF3	NM_003017.5	c.*600T>C		3_prime_UTR_variant	6/6	ENST00000373715.11	NP_003008.1
SRSF3	NR_036610.2	n.1673T>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRSF3	ENST00000373715.11	c.*600T>C		3_prime_UTR_variant	6/6	1	NM_003017.5	ENSP00000362820	P1
SRSF3	ENST00000614136.1	n.2187T>C		non_coding_transcript_exon_variant	1/1
SRSF3	ENST00000620389.1	n.2468T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30400 AN: 152086 Hom.: 3417 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.249 AC: 16252 AN: 65212 Hom.: 2336 Cov.: 0 AF XY: 0.248 AC XY: 7527 AN XY: 30324

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.479

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.200 AC: 30414 AN: 152204 Hom.: 3418 Cov.: 32 AF XY: 0.203 AC XY: 15122 AN XY: 74396

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.200

Alfa AF: 0.212 Hom.: 3929

Bravo AF: 0.189

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7344; hg19: chr6-36570366; COSMIC: COSV59672440; COSMIC: COSV59672440;