rs200870712

Variant names:

• chr3-125975636-T-C
• rs200870712
• NM_001308313.2:c.190T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001308313.2(ROPN1B):​c.190T>C​(p.Trp64Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,592,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: ROPN1B NM_001308313.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.058259934).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308313.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROPN1B	NM_001308313.2	MANE Select	c.190T>C	p.Trp64Arg	missense	Exon 4 of 7	NP_001295242.1	A0A140VKG6
	ROPN1B	NM_001012337.3		c.190T>C	p.Trp64Arg	missense	Exon 3 of 6	NP_001012337.1	A0A140VKG6
	ALG1L1P	NR_171196.1		n.116+14786A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROPN1B	ENST00000514116.6	TSL:1 MANE Select	c.190T>C	p.Trp64Arg	missense	Exon 4 of 7	ENSP00000426271.1	Q9BZX4-1
	ROPN1B	ENST00000251776.8	TSL:1	c.190T>C	p.Trp64Arg	missense	Exon 3 of 6	ENSP00000251776.4	Q9BZX4-1
	ROPN1B	ENST00000513830.5	TSL:2	c.190T>C	p.Trp64Arg	missense	Exon 5 of 6	ENSP00000425548.1	D6RCR2

Frequencies

GnomAD3 genomes AF: 0.000363 AC: 55 AN: 151488 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000581

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000139 AC: 35 AN: 251320 AF XY: 0.000155

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000103 AC: 149 AN: 1440564 Hom.: 0 Cov.: 31 AF XY: 0.000119 AC XY: 85 AN XY: 716958

African (AFR) AF: 0.000337 AC: 11 AN: 32636

American (AMR) AF: 0.0000454 AC: 2 AN: 44076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25090

East Asian (EAS) AF: 0.0000792 AC: 3 AN: 37890

South Asian (SAS) AF: 0.0000930 AC: 8 AN: 86032

European-Finnish (FIN) AF: 0.000155 AC: 8 AN: 51500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 0.000104 AC: 114 AN: 1098880

Other (OTH) AF: 0.0000510 AC: 3 AN: 58822

GnomAD4 genome AF: 0.000363 AC: 55 AN: 151610 Hom.: 0 Cov.: 32 AF XY: 0.000364 AC XY: 27 AN XY: 74140

African (AFR) AF: 0.000580 AC: 24 AN: 41412

American (AMR) AF: 0.000197 AC: 3 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5058

South Asian (SAS) AF: 0.000214 AC: 1 AN: 4672

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 67898

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.000321

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000288 AC: 35

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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	0.86
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.071
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.2
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.20
Sift	Benign	0.56	T
Sift4G	Benign	0.57	T
Polyphen		1.0	D
Vest4		0.76
MutPred		0.47		Gain of loop (P = 0.0045)
MVP		0.57
MPC		0.61
ClinPred		0.059	T
GERP RS		2.8
PromoterAI		0.026	Neutral
Varity_R		0.10
gMVP		0.55
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs200870712; hg19: chr3-125694479; COSMIC: COSV52541707; COSMIC: COSV52541707;