rs553499306

Variant names:

• chr2-185738911-G-A
• rs553499306
• NM_173651.4:c.17G>A

Variant summary

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

The NM_173651.4(FSIP2):​c.17G>A​(p.Gly6Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000293 in 1,535,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: FSIP2 NM_173651.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.853
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029123127).

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.17G>A	p.Gly6Asp	missense	Exon 1 of 23	NP_775922.3	Q5CZC0-1
	FSIP2-AS2	NR_110214.1		n.183C>T		non_coding_transcript_exon	Exon 1 of 4
	FSIP2-AS2	NR_110217.1		n.99+1468C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSIP2	ENST00000424728.6	TSL:5 MANE Select	c.17G>A	p.Gly6Asp	missense	Exon 1 of 23	ENSP00000401306.1	Q5CZC0-1
	FSIP2-AS1	ENST00000437717.1	TSL:3	n.115C>T		non_coding_transcript_exon	Exon 1 of 3
	FSIP2-AS1	ENST00000769855.1		n.183C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000101 AC: 13 AN: 128308 AF XY: 0.0000855

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000275 AC: 38 AN: 1382766 Hom.: 0 Cov.: 32 AF XY: 0.0000264 AC XY: 18 AN XY: 682318

African (AFR) AF: 0.00 AC: 0 AN: 31568

American (AMR) AF: 0.00 AC: 0 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.000812 AC: 29 AN: 35726

South Asian (SAS) AF: 0.0000758 AC: 6 AN: 79182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078702

Other (OTH) AF: 0.0000519 AC: 3 AN: 57826

GnomAD4 genome AF: 0.0000459 AC: 7 AN: 152350 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000480 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000528 AC: 1

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

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
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.059
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.85
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.080
Sift	Uncertain	0.013	D
Sift4G	Benign	0.081	T
Vest4		0.27
MVP		0.31
ClinPred		0.061	T
GERP RS		3.7
PromoterAI		-0.15	Neutral
Varity_R		0.15
gMVP		0.24
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs553499306; hg19: chr2-186603638;