XM_047444333.1:c.-507-571G>A

Variant names:

• chr2-185738775-G-A
• rs1418917210
• XM_047444333.1:c.-507-571G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The XM_047444333.1(FSIP2):​c.-507-571G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,383,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: FSIP2 XM_047444333.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.182
• Publications: 0 publications found

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.027).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000424728.6. 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-AS2	NR_110214.1		n.187+132C>T		intron	N/A
	FSIP2-AS2	NR_110217.1		n.99+1604C>T		intron	N/A
	FSIP2	NM_173651.4	MANE Select	c.-120G>A		upstream_gene	N/A	NP_775922.3	Q5CZC0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSIP2-AS1	ENST00000769859.1		n.211C>T		non_coding_transcript_exon	Exon 1 of 4
	FSIP2-AS1	ENST00000427269.2	TSL:5	n.101+1604C>T		intron	N/A
	FSIP2-AS1	ENST00000437717.1	TSL:3	n.119+132C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000289 AC: 4 AN: 1383660 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 682788

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.00 AC: 0 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1078772

Other (OTH) AF: 0.00 AC: 0 AN: 57894

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.92
PhyloP100		-0.18
PromoterAI		-0.61	Under-expression

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1418917210; hg19: chr2-186603502;