3-125972124-G-A

Variant names:

• chr3-125972124-G-A
• NM_001308313.2:c.70G>A

Variant summary

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

The NM_001308313.2(ROPN1B):​c.70G>A​(p.Ala24Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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)
• Consequence: ROPN1B NM_001308313.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55

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]

ENSG00000291096 (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 rank	MANE	Protein	UniProt
ROPN1B	NM_001308313.2	c.70G>A	p.Ala24Thr	missense_variant	Exon 3 of 7	ENST00000514116.6	NP_001295242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROPN1B	ENST00000514116.6	c.70G>A	p.Ala24Thr	missense_variant	Exon 3 of 7	1	NM_001308313.2	ENSP00000426271.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.70G>A (p.A24T) alteration is located in exon 2 (coding exon 1) of the ROPN1B gene. This alteration results from a G to A substitution at nucleotide position 70, causing the alanine (A) at amino acid position 24 to be replaced by a threonine (T). 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	0.20
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T;.;.;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.053
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.89	.;D;D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.49	T;T;T;T;T
MetaSVM	Uncertain	0.016	D
MutationAssessor	Pathogenic	3.1	M;M;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D
Polyphen		0.59	P;P;.;.;.
Vest4		0.51
MutPred		0.34		Gain of methylation at K19 (P = 0.0694);Gain of methylation at K19 (P = 0.0694);Gain of methylation at K19 (P = 0.0694);Gain of methylation at K19 (P = 0.0694);Gain of methylation at K19 (P = 0.0694);
MVP		0.90
MPC		0.44
ClinPred		0.96	D
GERP RS		3.4
Varity_R		0.35
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-125690967;