rs3104

Variant names:

• chr14-69769024-G-A
• rs3104
• NM_001320214.2:c.296+128G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-69769024-G-A
• chr14-69769024-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320214.2. 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
	SRSF5	NM_001320214.2	MANE Select	c.296+128G>A		intron	N/A	NP_001307143.1	Q13243-1
	SRSF5	NM_001039465.2		c.296+128G>A		intron	N/A	NP_001034554.1	Q13243-1
	SRSF5	NM_006925.5		c.296+128G>A		intron	N/A	NP_008856.2	Q13243-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF5	ENST00000557154.6	TSL:2 MANE Select	c.296+128G>A		intron	N/A	ENSP00000451088.1	Q13243-1
	SRSF5	ENST00000394366.6	TSL:1	c.296+128G>A		intron	N/A	ENSP00000377892.2	Q13243-1
	SRSF5	ENST00000553521.5	TSL:1	c.296+128G>A		intron	N/A	ENSP00000452123.1	Q13243-1

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

African (AFR) AF: 0.612 AC: 16080 AN: 26268

American (AMR) AF: 0.419 AC: 15693 AN: 37466

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 3826 AN: 23624

East Asian (EAS) AF: 0.145 AC: 5202 AN: 35946

South Asian (SAS) AF: 0.189 AC: 14427 AN: 76238

European-Finnish (FIN) AF: 0.270 AC: 13617 AN: 50382

Middle Eastern (MID) AF: 0.163 AC: 845 AN: 5176

European-Non Finnish (NFE) AF: 0.264 AC: 217648 AN: 823202

Other (OTH) AF: 0.267 AC: 13110 AN: 49150

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

African (AFR) AF: 0.611 AC: 25361 AN: 41490

American (AMR) AF: 0.400 AC: 6111 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3470

East Asian (EAS) AF: 0.162 AC: 843 AN: 5190

South Asian (SAS) AF: 0.193 AC: 929 AN: 4824

European-Finnish (FIN) AF: 0.272 AC: 2880 AN: 10572

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18175 AN: 67984

Other (OTH) AF: 0.355 AC: 751 AN: 2114

Alfa AF: 0.303 Hom.: 12164

Bravo AF: 0.384

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.070
DANN	Benign	0.57
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3104; hg19: chr14-70235741; COSMIC: COSV67936553; COSMIC: COSV67936553;