rs200870712

Variant names:

• chr3-125975636-T-A
• NM_001308313.2:c.190T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-125975636-T-A
• chr3-125975636-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001308313.2(ROPN1B):​c.190T>A​(p.Trp64Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 0.0000076 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ROPN1B NM_001308313.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27819064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROPN1B	NM_001308313.2	c.190T>A	p.Trp64Arg	missense_variant	Exon 4 of 7	ENST00000514116.6	NP_001295242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROPN1B	ENST00000514116.6	c.190T>A	p.Trp64Arg	missense_variant	Exon 4 of 7	1	NM_001308313.2	ENSP00000426271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000764 AC: 11 AN: 1440670 Hom.: 0 Cov.: 31 AF XY: 0.00000697 AC XY: 5 AN XY: 717016

Gnomad4 AFR exome AF: 0.0000613

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000399

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000546

Gnomad4 OTH exome AF: 0.0000340

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.89
DEOGEN2	Benign	0.0095	T;T;.;T
Eigen	Benign	-0.071
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.44	.;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	2.0	N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.56	T;T;T;T
Sift4G	Benign	0.57	T;T;T;T
Polyphen		1.0	D;D;.;.
Vest4		0.76
MutPred		0.47		Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);
MVP		0.57
MPC		0.61
ClinPred		0.75	D
GERP RS		2.8
Varity_R		0.10
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-125694479;