rs534671276

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001371194.2(SEMA4D):​c.1070G>T​(p.Arg357Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,451,974 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SEMA4D
NM_001371194.2 missense

Scores

8
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65
Variant links:
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]

Genome browser will be placed here

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

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEMA4DNM_001371194.2 linkc.1070G>T p.Arg357Leu missense_variant Exon 11 of 16 ENST00000422704.7 NP_001358123.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEMA4DENST00000422704.7 linkc.1070G>T p.Arg357Leu missense_variant Exon 11 of 16 1 NM_001371194.2 ENSP00000388768.2 Q92854-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000207
AC:
3
AN:
1451974
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
722586
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.030
T
BayesDel_noAF
Benign
-0.28
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
.;.;.;T;T;T;T
Eigen
Benign
0.066
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.89
.;D;.;.;.;D;.
M_CAP
Benign
0.025
D
MetaRNN
Uncertain
0.58
D;D;D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M;M;M;M;M;M;M
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.5
D;D;D;D;D;D;D
REVEL
Benign
0.12
Sift
Uncertain
0.026
D;D;D;D;D;D;D
Sift4G
Benign
0.062
T;T;T;T;T;T;T
Polyphen
0.0080
B;B;B;B;B;B;B
Vest4
0.76
MutPred
0.64
Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);Loss of MoRF binding (P = 0.0034);
MVP
0.40
MPC
0.40
ClinPred
0.98
D
GERP RS
4.7
Varity_R
0.81
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-92003588; API