NM_152594.3:c.939G>A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_152594.3(SPRED1):c.939G>A(p.Thr313Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000742 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_152594.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000769 AC: 117AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000537 AC: 135AN: 251194Hom.: 0 AF XY: 0.000545 AC XY: 74AN XY: 135754
GnomAD4 exome AF: 0.000739 AC: 1081AN: 1461822Hom.: 0 Cov.: 31 AF XY: 0.000748 AC XY: 544AN XY: 727206
GnomAD4 genome AF: 0.000768 AC: 117AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.00101 AC XY: 75AN XY: 74446
ClinVar
Submissions by phenotype
not provided Benign:4
This variant is associated with the following publications: (PMID: 28150585) -
Variant summary: The SPRED1 c.939G>A (p.Thr313Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of multiple ESE sites. However, no functional studies are available to confirm these predictions. This variant was found in 78/121206 control chromosomes from ExAC at a frequency of 0.0006435, which is approximately 257 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 benign. Taken together, this variant is classified as Benign. -
SPRED1: BP4, BP7 -
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not specified Benign:2
p.Thr313Thr in exon 7 of SPRED1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.1% (35/25780) of African American chromosomes by the Genome Aggregation Database (gnomAD, http:// gnomad.broadinstitute.org; dbSNP rs140644874). -
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Legius syndrome Benign:2
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
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Cardiovascular phenotype Benign:1
This alteration is classified as likely 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