NM_001317774.2:c.235-588C>T

Variant names:

• chr3-123976128-G-A
• rs6810298
• NM_001317774.2:c.235-588C>T

Variant summary

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

The NM_001317774.2(ROPN1):​c.235-588C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,028 control chromosomes in the GnomAD database, including 24,335 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 0.54 (24335 hom., cov: 31)
• Consequence: ROPN1 NM_001317774.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 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.235-588C>T		intron	N/A	NP_001304703.1
	ROPN1	NM_001394217.1		c.235-588C>T		intron	N/A	NP_001381146.1
	ROPN1	NM_001394218.1		c.235-588C>T		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.235-588C>T		intron	N/A	ENSP00000385919.3
	ROPN1	ENST00000184183.8	TSL:1	c.235-588C>T		intron	N/A	ENSP00000184183.4
	ROPN1	ENST00000620893.4	TSL:1	c.235-588C>T		intron	N/A	ENSP00000483603.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81597 AN: 151910 Hom.: 24334 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.537 AC: 81614 AN: 152028 Hom.: 24335 Cov.: 31 AF XY: 0.528 AC XY: 39245 AN XY: 74298

African (AFR) AF: 0.324 AC: 13435 AN: 41444

American (AMR) AF: 0.483 AC: 7385 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2194 AN: 3470

East Asian (EAS) AF: 0.113 AC: 585 AN: 5172

South Asian (SAS) AF: 0.509 AC: 2445 AN: 4808

European-Finnish (FIN) AF: 0.595 AC: 6288 AN: 10562

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47213 AN: 67978

Other (OTH) AF: 0.566 AC: 1196 AN: 2112

Alfa AF: 0.635 Hom.: 6281

Bravo AF: 0.515

Asia WGS AF: 0.305 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.59
PhyloP100		-0.14
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: rs6810298; hg19: chr3-123694975;