17-58007056-G-C

Variant names:

• chr17-58007056-G-C
• rs1477879201
• NM_006924.5:c.82C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP2 PP3

The NM_006924.5(SRSF1):​c.82C>G​(p.Arg28Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SRSF1 NM_006924.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.09
• Publications: 0 publications found

Genes affected

SRSF1 (HGNC:10780): (serine and arginine rich splicing factor 1) This gene encodes a member of the arginine/serine-rich splicing factor protein family. The encoded protein can either activate or repress splicing, depending on its phosphorylation state and its interaction partners. Multiple transcript variants have been found for this gene. There is a pseudogene of this gene on chromosome 13. [provided by RefSeq, Jun 2014]

SRSF1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Baylor College of Medicine Research Center, PanelApp Australia

ENSG00000266086 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 3.9581 (above the threshold of 3.09). Trascript score misZ: 5.8555 (above the threshold of 3.09). GenCC associations: The gene is linked to neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006924.5. 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
	SRSF1	NM_006924.5	MANE Select	c.82C>G	p.Arg28Gly	missense	Exon 1 of 4	NP_008855.1	Q07955-1
	SRSF1	NM_001078166.2		c.82C>G	p.Arg28Gly	missense	Exon 1 of 3	NP_001071634.1	Q07955-3
	SRSF1	NR_034041.2		n.191C>G		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF1	ENST00000258962.5	TSL:1 MANE Select	c.82C>G	p.Arg28Gly	missense	Exon 1 of 4	ENSP00000258962.4	Q07955-1
	ENSG00000266086	ENST00000578794.2	TSL:3	n.82C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000463235.2
	SRSF1	ENST00000581979.5	TSL:1	n.82C>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000463223.1	Q07955-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	29
DANN	Benign	0.95
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.1
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.040	D
Polyphen		0.41	B
Vest4		0.83
MutPred		0.46		Loss of stability (P = 0.0235)
MVP		0.76
MPC		2.6
ClinPred		1.0	D
GERP RS		5.1
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.96

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: rs1477879201; hg19: chr17-56084417;