5-9051902-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003966.3(SEMA5A):c.2816C>T(p.Pro939Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,613,926 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
SEMA5A
NM_003966.3 missense
NM_003966.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 6.32
Genes affected
SEMA5A (HGNC:10736): (semaphorin 5A) This gene belongs to the semaphorin gene family that encodes membrane proteins containing a semaphorin domain and several thrombospondin type-1 repeats. Members of this family are involved in axonal guidance during neural development. This gene has been implicated as an autism susceptibility gene.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152064Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251378Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135870
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461862Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 727234
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152064Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4AN XY: 74258
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 26, 2024 | The c.2816C>T (p.P939L) alteration is located in exon 20 (coding exon 18) of the SEMA5A gene. This alteration results from a C to T substitution at nucleotide position 2816, causing the proline (P) at amino acid position 939 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at