chr17-58006343-CAG-C

Variant names:

• chr17-58006343-CAG-C
• NM_006924.5:c.377_378delCT

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_006924.5(SRSF1):​c.377_378delCT​(p.Ser126TrpfsTer17) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRSF1 NM_006924.5 frameshift, splice_region
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.42
• Publications: 1 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: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-58006343-CAG-C is Pathogenic according to our data. Variant chr17-58006343-CAG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 2429775.Status of the report is criteria_provided_single_submitter, 1 stars.

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.377_378delCT	p.Ser126TrpfsTer17	frameshift splice_region	Exon 2 of 4	NP_008855.1	Q07955-1
	SRSF1	NM_001078166.2		c.377_378delCT	p.Ser126TrpfsTer17	frameshift splice_region	Exon 2 of 3	NP_001071634.1	Q07955-3
	SRSF1	NR_034041.2		n.486_487delCT		splice_region non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF1	ENST00000258962.5	TSL:1 MANE Select	c.377_378delCT	p.Ser126TrpfsTer17	frameshift splice_region	Exon 2 of 4	ENSP00000258962.4	Q07955-1
	ENSG00000266086	ENST00000578794.2	TSL:3	n.377_378delCT		splice_region non_coding_transcript_exon	Exon 2 of 6	ENSP00000463235.2
	SRSF1	ENST00000581979.5	TSL:1	n.377_378delCT		splice_region non_coding_transcript_exon	Exon 2 of 4	ENSP00000463223.1	Q07955-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Intellectual disability;C4022738:Neurodevelopmental delay (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.4

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

hg19: chr17-56083704; COSMIC: COSV105002944; COSMIC: COSV105002944;