NM_152594.3:c.-12G>A

Variant names:

• chr15-38253174-G-A
• rs371200183
• NM_152594.3:c.-12G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152594.3(SPRED1):​c.-12G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0000014 in 1,425,430 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPRED1 NM_152594.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• 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: Orphanet, Ambry Genetics, Genomics England PanelApp, ClinGen, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000310144 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED1	NM_152594.3	MANE Select	c.-12G>A		5_prime_UTR	Exon 1 of 7	NP_689807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED1	ENST00000299084.9	TSL:1 MANE Select	c.-12G>A		5_prime_UTR	Exon 1 of 7	ENSP00000299084.4
	SPRED1	ENST00000561205.1	TSL:5	n.327G>A		non_coding_transcript_exon	Exon 1 of 5
	ENSG00000310144	ENST00000847565.1		n.95+393C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000510 AC: 1 AN: 195970 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000120

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425430 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 705424

African (AFR) AF: 0.00 AC: 0 AN: 32678

American (AMR) AF: 0.00 AC: 0 AN: 40078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25506

East Asian (EAS) AF: 0.00 AC: 0 AN: 37852

South Asian (SAS) AF: 0.00 AC: 0 AN: 81370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1092678

Other (OTH) AF: 0.00 AC: 0 AN: 59070

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.97
PhyloP100		4.0
PromoterAI		-0.073	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs371200183; hg19: chr15-38545375;