2-74662778-G-A

Variant summary

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

The NM_004263.5(SEMA4F):​c.503G>A​(p.Gly168Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SEMA4F
NM_004263.5 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88
Variant links:
Genes affected
SEMA4F (HGNC:10734): (ssemaphorin 4F) This gene encodes a transmembrane class IV semaphorin family protein, which plays a role in neural development. This gene may be involved in neurogenesis in prostate cancer, the development of neurofibromas, and breast cancer tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

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/exons MANE Protein UniProt
SEMA4FNM_004263.5 linkuse as main transcriptc.503G>A p.Gly168Glu missense_variant 5/14 ENST00000357877.7 NP_004254.2 O95754-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SEMA4FENST00000357877.7 linkuse as main transcriptc.503G>A p.Gly168Glu missense_variant 5/141 NM_004263.5 ENSP00000350547.2 O95754-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251484
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461866
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1

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 submitterclinical testingAmbry GeneticsOct 03, 2022The c.503G>A (p.G168E) alteration is located in exon 5 (coding exon 5) of the SEMA4F gene. This alteration results from a G to A substitution at nucleotide position 503, causing the glycine (G) at amino acid position 168 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.;.
Eigen
Uncertain
0.66
Eigen_PC
Pathogenic
0.66
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.84
T;D;D
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.66
D;D;D
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.4
M;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-7.2
D;.;D
REVEL
Uncertain
0.30
Sift
Benign
0.27
T;.;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.86
P;.;D
Vest4
0.88
MVP
0.35
MPC
0.94
ClinPred
0.99
D
GERP RS
5.5
Varity_R
0.81
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.29
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.29
Position offset: 47

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs369113935; hg19: chr2-74889905; API