dbSNP rs369379081: FSIP2:p.Ile416Lys (chr2-185763189-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173651.4(FSIP2):c.1247T>A(p.Ile416Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000946 in 1,406,566 control chromosomes in the GnomAD database, including 1 homozygotes. 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. I416T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00059 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

FSIP2
NM_173651.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.75

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013007641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSIP2	NM_173651.4 link	c.1247T>A	p.Ile416Lys	missense_variant	Exon 12 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.1247T>A	p.Ile416Lys	missense_variant	Exon 12 of 23	5	NM_173651.4	ENSP00000401306.1		Q5CZC0-1

Frequencies

GnomAD3 genomes

AF:

0.000535

AC:

AN:

151448

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000956

AC:

AN:

135916

AF XY:

0.0000812

show subpopulations

Gnomad AFR exome

AF:

0.00171

Gnomad AMR exome

AF:

0.0000819

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000351

AC:

AN:

1255000

Hom.:

Cov.:

AF XY:

0.0000319

AC XY:

AN XY:

626386

show subpopulations

African (AFR)

AF:

0.00139

AC:

AN:

28880

American (AMR)

AF:

0.0000845

AC:

AN:

35516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24356

East Asian (EAS)

AF:

0.00

AC:

AN:

35174

South Asian (SAS)

AF:

0.00

AC:

AN:

76240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5452

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

962052

Other (OTH)

AF:

0.0000187

AC:

AN:

53508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000587

AC:

AN:

151566

Hom.:

Cov.:

AF XY:

0.000702

AC XY:

AN XY:

74072

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

41464

American (AMR)

AF:

0.000132

AC:

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67574

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000518

ExAC

AF:

0.0000564

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.0060

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.0021

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0096

LIST_S2

Benign

0.28

M_CAP

Benign

0.025

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-2.8

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

REVEL

Benign

0.029

Sift

Benign

0.30

Sift4G

Uncertain

0.059

Polyphen

0.36

Vest4

0.28

MutPred

0.34

Gain of ubiquitination at I416 (P = 0.006);

MVP

0.081

ClinPred

0.015

GERP RS

-5.1

Varity_R

0.035

gMVP

0.073

Mutation Taster

=99/1

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

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rs369379081

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over