6-36602589-T-C

Variant names:

• chr6-36602589-T-C
• rs7344
• NM_003017.5:c.*600T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003017.5(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 NM_003017.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003017.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF3	NM_003017.5	MANE Select	c.*600T>C		3_prime_UTR	Exon 6 of 6	NP_003008.1	P84103-1
	SRSF3	NR_036610.2		n.1673T>C		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF3	ENST00000373715.11	TSL:1 MANE Select	c.*600T>C		3_prime_UTR	Exon 6 of 6	ENSP00000362820.5	P84103-1
	SRSF3	ENST00000620941.2	TSL:3	c.*600T>C		3_prime_UTR	Exon 6 of 6	ENSP00000482833.1	P84103-1
	SRSF3	ENST00000855355.1		c.*600T>C		3_prime_UTR	Exon 6 of 6	ENSP00000525414.1

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

African (AFR) AF: 0.125 AC: 375 AN: 2996

American (AMR) AF: 0.156 AC: 312 AN: 2004

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 891 AN: 4102

East Asian (EAS) AF: 0.479 AC: 4531 AN: 9466

South Asian (SAS) AF: 0.196 AC: 110 AN: 560

European-Finnish (FIN) AF: 0.261 AC: 23 AN: 88

Middle Eastern (MID) AF: 0.162 AC: 64 AN: 396

European-Non Finnish (NFE) AF: 0.219 AC: 8785 AN: 40162

Other (OTH) AF: 0.213 AC: 1161 AN: 5438

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

African (AFR) AF: 0.122 AC: 5076 AN: 41562

American (AMR) AF: 0.181 AC: 2767 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 719 AN: 3468

East Asian (EAS) AF: 0.389 AC: 2016 AN: 5178

South Asian (SAS) AF: 0.214 AC: 1033 AN: 4832

European-Finnish (FIN) AF: 0.290 AC: 3066 AN: 10568

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15042 AN: 67984

Other (OTH) AF: 0.200 AC: 424 AN: 2116

Alfa AF: 0.208 Hom.: 5521

Bravo AF: 0.189

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.69
PhyloP100		0.092
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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