chr15-38351255-T-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_152594.3(SPRED1):āc.926T>Cā(p.Val309Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,614,108 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_152594.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00187 AC: 284AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000482 AC: 121AN: 251256Hom.: 1 AF XY: 0.000273 AC XY: 37AN XY: 135778
GnomAD4 exome AF: 0.000166 AC: 242AN: 1461838Hom.: 4 Cov.: 31 AF XY: 0.000139 AC XY: 101AN XY: 727212
GnomAD4 genome AF: 0.00187 AC: 284AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.00175 AC XY: 130AN XY: 74440
ClinVar
Submissions by phenotype
Legius syndrome Uncertain:2Benign:2
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
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not provided Benign:3
Variant summary: The SPRED1 c.926T>C (p.Val309Ala) variant involves the alteration of a conserved nucleotide and is predicted to be benign by 3/5 in silico tools. This variant was found in 81/121216 control chromosomes from ExAC at a frequency of 0.0006682, which is approximately 267 times the estimated maximal expected allele frequency of a pathogenic SPRED1 variant (0.0000025), therefore this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign/benign and it is also classified as likely benign in a publication with an indication of benign functional outcome (Brems_2012). Taken together, this variant is classified as benign. -
This variant is associated with the following publications: (PMID: 21548021, 22753041) -
SPRED1: BS1 -
not specified Benign:1
p.Val309Ala in Exon 07 of SPRED1: This variant is not expected to have clinical significance because it has been identified in 0.6% (21/3738) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs114636635). -
Cardiovascular phenotype Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Noonan syndrome and Noonan-related syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at