14-69769024-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001320214.2(SRSF5):​c.296+128G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000177 in 1,129,180 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: SRSF5 NM_001320214.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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>C		intron	N/A	NP_001307143.1	Q13243-1
	SRSF5	NM_001039465.2		c.296+128G>C		intron	N/A	NP_001034554.1	Q13243-1
	SRSF5	NM_006925.5		c.296+128G>C		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>C		intron	N/A	ENSP00000451088.1	Q13243-1
	SRSF5	ENST00000394366.6	TSL:1	c.296+128G>C		intron	N/A	ENSP00000377892.2	Q13243-1
	SRSF5	ENST00000553521.5	TSL:1	c.296+128G>C		intron	N/A	ENSP00000452123.1	Q13243-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000177 AC: 2 AN: 1129180 Hom.: 0 Cov.: 15 AF XY: 0.00000350 AC XY: 2 AN XY: 572214

African (AFR) AF: 0.00 AC: 0 AN: 26316

American (AMR) AF: 0.00 AC: 0 AN: 37480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23634

East Asian (EAS) AF: 0.00 AC: 0 AN: 35954

South Asian (SAS) AF: 0.00 AC: 0 AN: 76262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5178

European-Non Finnish (NFE) AF: 0.00000243 AC: 2 AN: 824722

Other (OTH) AF: 0.00 AC: 0 AN: 49206

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.056
DANN	Benign	0.43
PhyloP100		-2.4
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

Other links and lift over

dbSNP: rs3104; hg19: chr14-70235741;