Variant 5-10464882-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000274134.5(ROPN1L):c.628G>T(p.Asp210Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ROPN1L
ENST00000274134.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62

Variant links:

Genes affected

ROPN1L (HGNC:24060): (rhophilin associated tail protein 1 like) This gene encodes a member of the ropporin family. The encoded protein is present in sperm and interacts with A-kinase anchoring protein, AKAP3, through the amphipathic helix region of AKAP3. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2014]

ROPN1L links:

LOC124900940 (HGNC:):

LOC124900940 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROPN1L	NM_031916.5 linkuse as main transcript	c.628G>T	p.Asp210Tyr	missense_variant	5/5	ENST00000274134.5	NP_114122.2
LOC124900940	XM_047417967.1 linkuse as main transcript			downstream_gene_variant			XP_047273923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ROPN1L	ENST00000274134.5 linkuse as main transcript	c.628G>T	p.Asp210Tyr	missense_variant	5/5	1	NM_031916.5	ENSP00000274134	P1
ROPN1L	ENST00000503804.5 linkuse as main transcript	c.628G>T	p.Asp210Tyr	missense_variant	6/6	2		ENSP00000421405	P1
ROPN1L	ENST00000510520.5 linkuse as main transcript	n.885+3523G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454728

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723110

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Jun 10, 2024

The c.628G>T (p.D210Y) alteration is located in exon 5 (coding exon 5) of the ROPN1L gene. This alteration results from a G to T substitution at nucleotide position 628, causing the aspartic acid (D) at amino acid position 210 to be replaced by a tyrosine (Y). 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

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.0038

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.99

MutationAssessor

Pathogenic

3.0

M;M

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

1.0

D;D

Vest4

0.77

MutPred

0.47

Loss of ubiquitination at K215 (P = 0.0834);Loss of ubiquitination at K215 (P = 0.0834);

MVP

0.42

MPC

0.74

ClinPred

0.99

GERP RS

4.6

Varity_R

0.45

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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