3-125983295-A-G

Variant names:

• chr3-125983295-A-G
• NM_001308313.2:c.614A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308313.2(ROPN1B):​c.614A>G​(p.Gln205Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ROPN1B NM_001308313.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19334435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROPN1B	NM_001308313.2	c.614A>G	p.Gln205Arg	missense_variant	Exon 7 of 7	ENST00000514116.6	NP_001295242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROPN1B	ENST00000514116.6	c.614A>G	p.Gln205Arg	missense_variant	Exon 7 of 7	1	NM_001308313.2	ENSP00000426271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.0042	T;T;.;.
Eigen	Benign	0.071
Eigen_PC	Benign	0.018
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.62	.;T;.;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.53	T;T;T;T
Sift4G	Benign	0.86	T;T;T;T
Polyphen		0.91	P;P;.;.
Vest4		0.30
MutPred		0.33		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);.;.;
MVP		0.27
MPC		1.0
ClinPred		0.65	D
GERP RS		2.2
Varity_R		0.14
gMVP		0.25

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: chr3-125702138;