Genetic Variant FSIP2:p.Lys139Asn (chr2-185744351-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_173651.4(FSIP2):c.417G>T(p.Lys139Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000091 in 1,099,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K139K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

FSIP2
NM_173651.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.629

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3411821).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSIP2	NM_173651.4	MANE Select	c.417G>T	p.Lys139Asn	missense	Exon 4 of 23	NP_775922.3	Q5CZC0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FSIP2	ENST00000424728.6	TSL:5 MANE Select	c.417G>T	p.Lys139Asn	missense	Exon 4 of 23	ENSP00000401306.1	Q5CZC0-1
FSIP2	ENST00000469367.1	TSL:3	n.142G>T		non_coding_transcript_exon	Exon 2 of 2
FSIP2-AS1	ENST00000667756.2		n.247+44415C>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.10e-7

AC:

AN:

1099362

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

545384

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

22668

American (AMR)

AF:

0.00

AC:

AN:

14106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18742

East Asian (EAS)

AF:

0.00

AC:

AN:

28442

South Asian (SAS)

AF:

0.00

AC:

AN:

49898

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4808

European-Non Finnish (NFE)

AF:

0.00000113

AC:

AN:

887490

Other (OTH)

AF:

0.00

AC:

AN:

45880

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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

Pathogenic

0.82

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.75

M_CAP

Benign

0.025

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

PhyloP100

0.63

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.079

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Vest4

0.37

MVP

0.46

ClinPred

0.94

GERP RS

0.91

Varity_R

0.31

gMVP

0.11

Mutation Taster

=78/22

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