9-89376938-C-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The ENST00000450295.5(SEMA4D):c.*1766G>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000428 in 1,550,768 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 Benign (★).
Frequency
Genomes: 𝑓 0.0024 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00022 ( 0 hom. )
Consequence
SEMA4D
ENST00000450295.5 3_prime_UTR
ENST00000450295.5 3_prime_UTR
Scores
4
10
Clinical Significance
Conservation
PhyloP100: 5.09
Genes affected
SEMA4D (HGNC:10732): (semaphorin 4D) Enables identical protein binding activity; semaphorin receptor binding activity; and transmembrane signaling receptor activity. Involved in several processes, including positive regulation of phosphatidylinositol 3-kinase signaling; regulation of neuron projection development; and regulation of phosphate metabolic process. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0060606897).
BP6
?
Variant 9-89376938-C-A is Benign according to our data. Variant chr9-89376938-C-A is described in ClinVar as [Benign]. Clinvar id is 3049327.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA4D | NM_001142287.2 | c.1777G>T | p.Gly593Trp | missense_variant | 18/21 | ||
SEMA4D | NM_001371198.1 | c.1777G>T | p.Gly593Trp | missense_variant | 16/19 | ||
SEMA4D | NM_001371199.1 | c.1777G>T | p.Gly593Trp | missense_variant | 17/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA4D | ENST00000450295.5 | c.*1766G>T | 3_prime_UTR_variant | 16/16 | 1 | P1 | |||
SEMA4D | ENST00000339861.8 | c.1777G>T | p.Gly593Trp | missense_variant | 16/19 | 5 | |||
SEMA4D | ENST00000420987.5 | c.1777G>T | p.Gly593Trp | missense_variant | 17/20 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00236 AC: 359AN: 152190Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000464 AC: 71AN: 153112Hom.: 0 AF XY: 0.000344 AC XY: 28AN XY: 81462
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GnomAD4 exome AF: 0.000217 AC: 303AN: 1398460Hom.: 0 Cov.: 32 AF XY: 0.000193 AC XY: 133AN XY: 689746
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GnomAD4 genome ? AF: 0.00236 AC: 360AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.00199 AC XY: 148AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
SEMA4D-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 28, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N;N;N
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MVP
ClinPred
T
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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