2-185791079-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173651.4(FSIP2):​c.3943G>C​(p.Glu1315Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.2e-7 ( 0 hom. )

Consequence

FSIP2
NM_173651.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.217
Variant links:
Genes affected
FSIP2 (HGNC:21675): (fibrous sheath interacting protein 2) This gene encodes a protein associated with the sperm fibrous sheath. Genes encoding most of the fibrous-sheath associated proteins genes are transcribed only during the postmeiotic period of spermatogenesis. The protein encoded by this gene is specific to spermatogenic cells. Copy number variation in this gene may be associated with testicular germ cell tumors. Pseudogenes associated with this gene are reported on chromosomes 2 and X. [provided by RefSeq, Aug 2016]
FSIP2-AS1 (HGNC:40978): (FSIP2 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.057944447).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FSIP2NM_173651.4 linkc.3943G>C p.Glu1315Gln missense_variant Exon 16 of 23 ENST00000424728.6 NP_775922.3 Q5CZC0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FSIP2ENST00000424728.6 linkc.3943G>C p.Glu1315Gln missense_variant Exon 16 of 23 5 NM_173651.4 ENSP00000401306.1 Q5CZC0-1
FSIP2-AS1ENST00000429929.1 linkn.73-2136C>G intron_variant Intron 1 of 2 3
FSIP2-AS1ENST00000436557.5 linkn.72-2136C>G intron_variant Intron 1 of 2 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.24e-7
AC:
1
AN:
1380344
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
681082
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:
9.28e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
2.1
DANN
Benign
0.79
DEOGEN2
Benign
0.0010
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.058
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.35
N
REVEL
Benign
0.014
Sift
Benign
0.26
T
Sift4G
Benign
0.30
T
Vest4
0.088
MVP
0.072
ClinPred
0.13
T
GERP RS
0.13
Varity_R
0.047
gMVP
0.049

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr2-186655806; API