Genetic Variant FSIP2:c.-11C>T (chr2-185738884-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_173651.4(FSIP2):c.-11C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000527 in 1,523,138 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 5 hom. )

Consequence

FSIP2
NM_173651.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0380

Publications

1 publications found

Variant links:

COSMIC-nc: COSV58093250

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:

FSIP2-AS2 (HGNC:54061): (FSIP2 antisense RNA 2)

FSIP2-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.008).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

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	Effect	Exon Rank	Protein	UniProt
FSIP2	NM_173651.4	MANE Select	c.-11C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 23	NP_775922.3	Q5CZC0-1
FSIP2	NM_173651.4	MANE Select	c.-11C>T	5_prime_UTR	Exon 1 of 23	NP_775922.3	Q5CZC0-1
FSIP2-AS2	NR_110214.1		n.187+23G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FSIP2	ENST00000424728.6	TSL:5 MANE Select	c.-11C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 23	ENSP00000401306.1	Q5CZC0-1
FSIP2	ENST00000424728.6	TSL:5 MANE Select	c.-11C>T	5_prime_UTR	Exon 1 of 23	ENSP00000401306.1	Q5CZC0-1
FSIP2-AS1	ENST00000769859.1		n.102G>A	non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

149944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000134

Gnomad ASJ

AF:

0.00613

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00273

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.000402

Gnomad OTH

AF:

0.000979

GnomAD2 exomes

AF:

0.000833

AC:

107

AN:

128406

AF XY:

0.000883

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00507

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000535

AC:

735

AN:

1373066

Hom.:

Cov.:

AF XY:

0.000636

AC XY:

431

AN XY:

677674

show subpopulations

African (AFR)

AF:

0.0000319

AC:

AN:

31356

American (AMR)

AF:

0.0000579

AC:

AN:

34564

Ashkenazi Jewish (ASJ)

AF:

0.00575

AC:

141

AN:

24504

East Asian (EAS)

AF:

0.00

AC:

AN:

35658

South Asian (SAS)

AF:

0.00255

AC:

200

AN:

78378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33496

Middle Eastern (MID)

AF:

0.00597

AC:

AN:

5362

European-Non Finnish (NFE)

AF:

0.000291

AC:

312

AN:

1072330

Other (OTH)

AF:

0.000819

AC:

AN:

57418

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

143

190

238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000446

AC:

AN:

150072

Hom.:

Cov.:

AF XY:

0.000463

AC XY:

AN XY:

73362

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

40928

American (AMR)

AF:

0.000134

AC:

AN:

14980

Ashkenazi Jewish (ASJ)

AF:

0.00613

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

5066

South Asian (SAS)

AF:

0.00274

AC:

AN:

4752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10482

Middle Eastern (MID)

AF:

0.00350

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000402

AC:

AN:

67184

Other (OTH)

AF:

0.000968

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000374

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.4

(source)

DANN

Uncertain

1.0

PhyloP100

-0.038

PromoterAI

-0.0026

Neutral

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over