Variant 3-125982349-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000514116.6(ROPN1B):c.476G>A(p.Ser159Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,090 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: 6.8e-7 ( 0 hom. )

Consequence

ROPN1B
ENST00000514116.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Variant links:

Genes affected

ROPN1B (HGNC:31927): (rhophilin associated tail protein 1B) Enables protein heterodimerization activity. Predicted to be involved in several processes, including flagellated sperm motility; protein localization to cilium; and sperm capacitation. Located in cytoplasm and motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

ROPN1B links:

ALG1L1P (HGNC:33721): (ALG1 like 1, pseudogene) Predicted to enable mannosyltransferase activity. Predicted to be involved in protein glycosylation. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ALG1L1P links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3870398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROPN1B	NM_001308313.2 linkuse as main transcript	c.476G>A	p.Ser159Asn	missense_variant	6/7	ENST00000514116.6	NP_001295242.1
ALG1L1P	NR_171197.1 linkuse as main transcript	n.116+8073C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ROPN1B	ENST00000514116.6 linkuse as main transcript	c.476G>A	p.Ser159Asn	missense_variant	6/7	1	NM_001308313.2	ENSP00000426271	Q9BZX4-1
ALG1L1P	ENST00000611639.4 linkuse as main transcript	n.116+8073C>T		intron_variant, non_coding_transcript_variant		3
	ENST00000692801.1 linkuse as main transcript	n.152+8073C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461090

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726842

show subpopulations

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:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

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

Feb 23, 2023

The c.476G>A (p.S159N) alteration is located in exon 5 (coding exon 4) of the ROPN1B gene. This alteration results from a G to A substitution at nucleotide position 476, causing the serine (S) at amino acid position 159 to be replaced by an asparagine (N). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0080

T;T;.;.

Eigen

Benign

0.17

Eigen_PC

Benign

0.058

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.76

.;T;.;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.39

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;.;.

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.69

N;N;N;N

REVEL

Benign

0.089

Sift

Benign

0.22

T;T;T;T

Sift4G

Benign

0.53

T;T;T;T

Polyphen

0.98

D;D;.;.

Vest4

0.59

MutPred

0.27

Loss of glycosylation at S159 (P = 0.0171);Loss of glycosylation at S159 (P = 0.0171);.;.;

MVP

0.29

MPC

0.56

ClinPred

0.76

GERP RS

2.4

Varity_R

0.087

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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