15-38253023-TG-TGGG

Variant names:

• chr15-38253023-T-TGG
• rs531519324
• NM_152594.3:c.-157_-156dupGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152594.3(SPRED1):​c.-157_-156dupGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000192 in 520,054 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: SPRED1 NM_152594.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• Publications: 0 publications found

Genes affected

SPRED1 (HGNC:20249): (sprouty related EVH1 domain containing 1) The protein encoded by this gene is a member of the Sprouty family of proteins and is phosphorylated by tyrosine kinase in response to several growth factors. The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade. Defects in this gene are a cause of neurofibromatosis type 1-like syndrome (NFLS). [provided by RefSeq, Jul 2008]

SPRED1 Gene-Disease associations (from GenCC):

• Legius syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, PanelApp Australia

ENSG00000310144 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152594.3. 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
	SPRED1	NM_152594.3	MANE Select	c.-157_-156dupGG		5_prime_UTR	Exon 1 of 7	NP_689807.1	Q7Z699

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED1	ENST00000299084.9	TSL:1 MANE Select	c.-157_-156dupGG		5_prime_UTR	Exon 1 of 7	ENSP00000299084.4	Q7Z699
	SPRED1	ENST00000881380.1		c.-157_-156dupGG		5_prime_UTR	Exon 1 of 8	ENSP00000551439.1
	SPRED1	ENST00000951939.1		c.-157_-156dupGG		5_prime_UTR	Exon 1 of 8	ENSP00000621998.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000192 AC: 1 AN: 520054 Hom.: 0 Cov.: 6 AF XY: 0.00000360 AC XY: 1 AN XY: 277818

African (AFR) AF: 0.00 AC: 0 AN: 14724

American (AMR) AF: 0.00 AC: 0 AN: 28920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17170

East Asian (EAS) AF: 0.00 AC: 0 AN: 31478

South Asian (SAS) AF: 0.0000177 AC: 1 AN: 56436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 308158

Other (OTH) AF: 0.00 AC: 0 AN: 28768

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs531519324; hg19: chr15-38545224;