ENST00000504401.1:c.115G>C

Variant names:

• chr3-125972169-G-C
• rs143434891
• ENST00000504401.1:c.115G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000504401.1(ROPN1B):​c.115G>C​(p.Glu39Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: ROPN1B ENST00000504401.1 missense
• Scores: Splicing: ADA: 0.006883
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.10
• Publications: 0 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]

ENSG00000291096 (HGNC:):

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25442517).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000504401.1. 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.115G>C	p.Asp39His	missense splice_region	Exon 3 of 7	NP_001295242.1	A0A140VKG6
	ROPN1B	NM_001012337.3		c.115G>C	p.Asp39His	missense splice_region	Exon 2 of 6	NP_001012337.1	A0A140VKG6
	ALG1L1P	NR_171196.1		n.116+18253C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROPN1B	ENST00000504401.1	TSL:1	c.115G>C	p.Glu39Gln	missense	Exon 2 of 2	ENSP00000424457.1	D6RAA3
	ROPN1B	ENST00000514116.6	TSL:1 MANE Select	c.115G>C	p.Asp39His	missense splice_region	Exon 3 of 7	ENSP00000426271.1	Q9BZX4-1
	ROPN1B	ENST00000251776.8	TSL:1	c.115G>C	p.Asp39His	missense splice_region	Exon 2 of 6	ENSP00000251776.4	Q9BZX4-1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152226 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251212 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461766 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727188

African (AFR) AF: 0.000239 AC: 8 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111902

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152226 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8 AN XY: 74370

African (AFR) AF: 0.000362 AC: 15 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000125

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.19
Sift	Benign	0.071	T
Sift4G	Benign	0.073	T
Polyphen		0.94	P
Vest4		0.47
MVP		0.85
MPC		0.26
ClinPred		0.17	T
GERP RS		3.4
Varity_R		0.16
gMVP		0.55
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0069
dbscSNV1_RF	Benign	0.052
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: rs143434891; hg19: chr3-125691012;