Variant 2-185738884-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_173651.4(FSIP2):c.-11C>T variant causes a 5 prime UTR 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0380

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

FSIP2-AS2 links:

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

FSIP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000446 (67/150072) while in subpopulation SAS AF= 0.00274 (13/4752). AF 95% confidence interval is 0.00162. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSIP2	NM_173651.4 linkuse as main transcript	c.-11C>T		5_prime_UTR_variant	1/23	ENST00000424728.6	NP_775922.3
FSIP2-AS2	NR_110217.1 linkuse as main transcript	n.99+1495G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSIP2	ENST00000424728.6 linkuse as main transcript	c.-11C>T	5_prime_UTR_variant	1/23	5	NM_173651.4	ENSP00000401306	P1	Q5CZC0-1
FSIP2-AS2	ENST00000427269.2 linkuse as main transcript	n.101+1495G>A	intron_variant, non_coding_transcript_variant		5
FSIP2-AS1	ENST00000667756.1 linkuse as main transcript	n.37+49882G>A	intron_variant, non_coding_transcript_variant
FSIP2-AS2	ENST00000437717.1 linkuse as main transcript	n.119+23G>A	intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes

AF:

0.000833

AC:

107

AN:

128406

Hom.:

AF XY:

0.000883

AC XY:

AN XY:

70246

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 SAS exome

AF:

0.00201

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

Gnomad4 AFR exome

AF:

0.0000319

Gnomad4 AMR exome

AF:

0.0000579

Gnomad4 ASJ exome

AF:

0.00575

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000291

Gnomad4 OTH exome

AF:

0.000819

GnomAD4 genome

AF:

0.000446

AC:

AN:

150072

Hom.:

Cov.:

AF XY:

0.000463

AC XY:

AN XY:

73362

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.000134

Gnomad4 ASJ

AF:

0.00613

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00274

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000402

Gnomad4 OTH

AF:

0.000968

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000374

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2023

The c.257C>T (p.A86V) alteration is located in exon 1 (coding exon 1) of the FSIP2 gene. This alteration results from a C to T substitution at nucleotide position 257, causing the alanine (A) at amino acid position 86 to be replaced by a valine (V). 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

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.4

DANN

Uncertain

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over