chr3-125972089-C-A

Position:

• chr3-125972089-C-A

Variant summary

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

The ENST00000514116.6(ROPN1B):​c.35C>A​(p.Pro12Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ROPN1B ENST00000514116.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02

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]

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]

(HGNC:):

ACMG classification

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
ROPN1B	NM_001308313.2	c.35C>A	p.Pro12Gln	missense_variant	3/7	ENST00000514116.6	NP_001295242.1
ALG1L1P	NR_171197.1	n.116+18333G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROPN1B	ENST00000514116.6	c.35C>A	p.Pro12Gln	missense_variant	3/7	1	NM_001308313.2	ENSP00000426271
ALG1L1P	ENST00000611639.4	n.116+18333G>T		intron_variant, non_coding_transcript_variant		3
	ENST00000692801.1	n.152+18333G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2023

The c.35C>A (p.P12Q) alteration is located in exon 2 (coding exon 1) of the ROPN1B gene. This alteration results from a C to A substitution at nucleotide position 35, causing the proline (P) at amino acid position 12 to be replaced by a glutamine (Q). 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	Benign	0.10
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T;T;.;.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.80	.;T;T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.7	M;M;.;.;.
MutationTaster	Benign	0.62	N;N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.5	D;D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		1.0	D;D;.;.;.
Vest4		0.51
MutPred		0.61		Loss of catalytic residue at P11 (P = 0.0401);Loss of catalytic residue at P11 (P = 0.0401);Loss of catalytic residue at P11 (P = 0.0401);Loss of catalytic residue at P11 (P = 0.0401);Loss of catalytic residue at P11 (P = 0.0401);
MVP		0.74
MPC		0.64
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.80
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-125690932;