Genetic Variant NM_173651.4:c.3943G>C (chr2-185791079-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1315K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

FSIP2
NM_173651.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.217

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057944447).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173651.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FSIP2	NM_173651.4	MANE Select	c.3943G>C	p.Glu1315Gln	missense	Exon 16 of 23	NP_775922.3
FSIP2-AS1	NR_144453.1		n.72-2136C>G		intron	N/A
FSIP2-AS1	NR_144454.1		n.73-2136C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FSIP2	ENST00000424728.6	TSL:5 MANE Select	c.3943G>C	p.Glu1315Gln	missense	Exon 16 of 23	ENSP00000401306.1
FSIP2-AS1	ENST00000429929.1	TSL:3	n.73-2136C>G		intron	N/A
FSIP2-AS1	ENST00000436557.5	TSL:3	n.72-2136C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.24e-7

AC:

AN:

1380344

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

681082

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31384

American (AMR)

AF:

0.00

AC:

AN:

35404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24938

East Asian (EAS)

AF:

0.00

AC:

AN:

35680

South Asian (SAS)

AF:

0.00

AC:

AN:

78654

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33772

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077148

Other (OTH)

AF:

0.00

AC:

AN:

57714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

2.1

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0010

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.54

M_CAP

Benign

0.0092

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.22

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.35

REVEL

Benign

0.014

Sift

Benign

0.26

Sift4G

Benign

0.30

Vest4

0.088

MVP

0.072

ClinPred

0.13

GERP RS

0.13

Varity_R

0.047

gMVP

0.049

Mutation Taster

=98/2

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over