Genetic Variant FSIP2:p.Val384Phe (chr2-185761059-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173651.4(FSIP2):c.1150G>T(p.Val384Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000741 in 1,348,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

FSIP2
NM_173651.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.640

Publications

0 publications found

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 links:

FSIP2-AS1 (HGNC:40978): (FSIP2 antisense RNA 1)

FSIP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0696933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSIP2	NM_173651.4 link	c.1150G>T	p.Val384Phe	missense_variant	Exon 10 of 23	ENST00000424728.6	NP_775922.3	Q5CZC0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSIP2	ENST00000424728.6 link	c.1150G>T	p.Val384Phe	missense_variant	Exon 10 of 23	5	NM_173651.4	ENSP00000401306.1		Q5CZC0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.41e-7

AC:

AN:

1348806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

666950

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30196

American (AMR)

AF:

0.00

AC:

AN:

34964

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24672

East Asian (EAS)

AF:

0.00

AC:

AN:

35238

South Asian (SAS)

AF:

0.00

AC:

AN:

77042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5498

European-Non Finnish (NFE)

AF:

9.51e-7

AC:

AN:

1051128

Other (OTH)

AF:

0.00

AC:

AN:

56438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 27, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1417G>T (p.V473F) alteration is located in exon 10 (coding exon 10) of the FSIP2 gene. This alteration results from a G to T substitution at nucleotide position 1417, causing the valine (V) at amino acid position 473 to be replaced by a phenylalanine (F). 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

Benign

0.10

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.91

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0059

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.33

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-0.64

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.1

REVEL

Benign

0.10

Sift

Uncertain

0.017

Sift4G

Uncertain

0.013

Polyphen

0.025

Vest4

0.27

MutPred

0.22

Loss of MoRF binding (P = 0.1081);

MVP

0.092

ClinPred

0.042

GERP RS

-2.1

Varity_R

0.071

gMVP

0.075

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over