dbSNP rs3104: SRSF5:c.296+128G>A (chr14-69769024-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.38

Variant links:

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]

SRSF5 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF5	NM_001320214.2 link	c.296+128G>A		intron_variant	Intron 4 of 7	ENST00000557154.6	NP_001307143.1	Q13243-1A0A024R6D8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF5	ENST00000557154.6 link	c.296+128G>A		intron_variant	Intron 4 of 7	2	NM_001320214.2	ENSP00000451088.1		Q13243-1

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55782

AN:

152014

Hom.:

12237

Cov.:

show subpopulations

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.:

AF XY:

0.262

AC XY:

149754

AN XY:

571396

show subpopulations

Gnomad4 AFR exome

AF:

0.612

AC:

16080

AN:

26268

Gnomad4 AMR exome

AF:

0.419

AC:

15693

AN:

37466

Gnomad4 ASJ exome

AF:

0.162

AC:

3826

AN:

23624

Gnomad4 EAS exome

AF:

0.145

AC:

5202

AN:

35946

Gnomad4 SAS exome

AF:

0.189

AC:

14427

AN:

76238

Gnomad4 FIN exome

AF:

0.270

AC:

13617

AN:

50382

Gnomad4 NFE exome

AF:

0.264

AC:

217648

AN:

823202

Gnomad4 Remaining exome

AF:

0.267

AC:

13110

AN:

49150

Heterozygous variant carriers

11750

23500

35250

47000

58750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

6530

13060

19590

26120

32650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.367

AC:

55902

AN:

152132

Hom.:

12289

Cov.:

AF XY:

0.364

AC XY:

27063

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.611

AC:

0.611256

AN:

0.611256

Gnomad4 AMR

AF:

0.400

AC:

0.39983

AN:

0.39983

Gnomad4 ASJ

AF:

0.164

AC:

0.163977

AN:

0.163977

Gnomad4 EAS

AF:

0.162

AC:

0.162428

AN:

0.162428

Gnomad4 SAS

AF:

0.193

AC:

0.192579

AN:

0.192579

Gnomad4 FIN

AF:

0.272

AC:

0.272418

AN:

0.272418

Gnomad4 NFE

AF:

0.267

AC:

0.267342

AN:

0.267342

Gnomad4 OTH

AF:

0.355

AC:

0.355251

AN:

0.355251

Heterozygous variant carriers

1636

3272

4907

6543

8179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over