NM_001317774.2:c.-12-483T>G

Variant names:

• chr3-123980976-A-C
• rs17310770
• NM_001317774.2:c.-12-483T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001317774.2(ROPN1):​c.-12-483T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,218 control chromosomes in the GnomAD database, including 1,246 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1246 hom., cov: 32)
• Consequence: ROPN1 NM_001317774.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19
• Publications: 5 publications found

Genes affected

ROPN1 (HGNC:17692): (rhophilin associated tail protein 1) The protein encoded by this gene is found in the fibrous sheath of spermatazoa, where it interacts with rhophilin, a Rho GTPase binding protein. The encoded protein also can bind an A-kinase anchoring protein (AKAP110) and a calcium-binding tyrosine phosphorylation-regulated protein (CABYR). This protein may be involved in sperm motility and has been shown to be a cancer-testis antigen in hematologic malignancies. Several transcript variants, some protein-coding and some non-protein coding, have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317774.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROPN1	NM_001317774.2	MANE Select	c.-12-483T>G		intron	N/A	NP_001304703.1
	ROPN1	NM_001394217.1		c.-13+403T>G		intron	N/A	NP_001381146.1
	ROPN1	NM_001394218.1		c.-123-372T>G		intron	N/A	NP_001381147.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROPN1	ENST00000405845.8	TSL:1 MANE Select	c.-12-483T>G		intron	N/A	ENSP00000385919.3
	ROPN1	ENST00000184183.8	TSL:1	c.-123-372T>G		intron	N/A	ENSP00000184183.4
	ROPN1	ENST00000459660.5	TSL:1	c.-13+403T>G		intron	N/A	ENSP00000420590.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17298 AN: 152100 Hom.: 1244 Cov.: 32

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17301 AN: 152218 Hom.: 1246 Cov.: 32 AF XY: 0.114 AC XY: 8502 AN XY: 74418

African (AFR) AF: 0.0312 AC: 1295 AN: 41546

American (AMR) AF: 0.104 AC: 1589 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3466

East Asian (EAS) AF: 0.104 AC: 541 AN: 5180

South Asian (SAS) AF: 0.201 AC: 970 AN: 4814

European-Finnish (FIN) AF: 0.134 AC: 1424 AN: 10596

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10473 AN: 68002

Other (OTH) AF: 0.128 AC: 271 AN: 2110

Alfa AF: 0.144 Hom.: 3147

Bravo AF: 0.107

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.60
PhyloP100		3.2
PromoterAI		-0.0047	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs17310770; hg19: chr3-123699823;