14-69768861-C-A

Variant names:

• chr14-69768861-C-A
• rs1467710301
• NM_001320214.2:c.261C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001320214.2(SRSF5):​c.261C>A​(p.Asp87Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SRSF5 NM_001320214.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.981
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2025361).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.261C>A	p.Asp87Glu	missense	Exon 4 of 8	NP_001307143.1	Q13243-1
	SRSF5	NM_001039465.2		c.261C>A	p.Asp87Glu	missense	Exon 4 of 8	NP_001034554.1	Q13243-1
	SRSF5	NM_006925.5		c.261C>A	p.Asp87Glu	missense	Exon 4 of 8	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.261C>A	p.Asp87Glu	missense	Exon 4 of 8	ENSP00000451088.1	Q13243-1
	SRSF5	ENST00000394366.6	TSL:1	c.261C>A	p.Asp87Glu	missense	Exon 4 of 8	ENSP00000377892.2	Q13243-1
	SRSF5	ENST00000553521.5	TSL:1	c.261C>A	p.Asp87Glu	missense	Exon 5 of 9	ENSP00000452123.1	Q13243-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.98
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.072
Sift	Benign	0.18	T
Sift4G	Benign	0.39	T
Polyphen		0.50	P
Vest4		0.33
MutPred		0.28		Gain of catalytic residue at Y85 (P = 0.0891)
MVP		0.54
MPC		1.1
ClinPred		0.32	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.075
gMVP		0.42
Mutation Taster		=88/12	polymorphism

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: rs1467710301; hg19: chr14-70235578;