chr3-125977110-C-T

Variant names:

• chr3-125977110-C-T
• rs201958681
• NM_001308313.2:c.341C>T

Variant summary

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

The NM_001308313.2(ROPN1B):​c.341C>T​(p.Thr114Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000432 in 150,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00057 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ROPN1B NM_001308313.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.687
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01631406).

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.341C>T	p.Thr114Met	missense	Exon 5 of 7	NP_001295242.1	A0A140VKG6
	ROPN1B	NM_001012337.3		c.341C>T	p.Thr114Met	missense	Exon 4 of 6	NP_001012337.1	A0A140VKG6
	ALG1L1P	NR_171196.1		n.116+13312G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROPN1B	ENST00000514116.6	TSL:1 MANE Select	c.341C>T	p.Thr114Met	missense	Exon 5 of 7	ENSP00000426271.1	Q9BZX4-1
	ROPN1B	ENST00000251776.8	TSL:1	c.341C>T	p.Thr114Met	missense	Exon 4 of 6	ENSP00000251776.4	Q9BZX4-1
	ROPN1B	ENST00000513830.5	TSL:2	c.341C>T	p.Thr114Met	missense	Exon 6 of 6	ENSP00000425548.1	D6RCR2

Frequencies

GnomAD3 genomes AF: 0.000432 AC: 65 AN: 150356 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000742

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000670

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000782

Gnomad OTH AF: 0.000491

GnomAD2 exomes AF: 0.000606 AC: 100 AN: 165046 AF XY: 0.000671

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000828

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000638

Gnomad FIN exome AF: 0.000241

Gnomad NFE exome AF: 0.00126

Gnomad OTH exome AF: 0.000497

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000573 AC: 568 AN: 990842 Hom.: 1 Cov.: 13 AF XY: 0.000540 AC XY: 276 AN XY: 510646

African (AFR) AF: 0.0000888 AC: 2 AN: 22510

American (AMR) AF: 0.000119 AC: 5 AN: 42126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21700

East Asian (EAS) AF: 0.0000530 AC: 2 AN: 37718

South Asian (SAS) AF: 0.0000137 AC: 1 AN: 73228

European-Finnish (FIN) AF: 0.000728 AC: 38 AN: 52216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3758

European-Non Finnish (NFE) AF: 0.000712 AC: 493 AN: 692752

Other (OTH) AF: 0.000602 AC: 27 AN: 44834

GnomAD4 genome AF: 0.000432 AC: 65 AN: 150474 Hom.: 0 Cov.: 29 AF XY: 0.000449 AC XY: 33 AN XY: 73474

African (AFR) AF: 0.0000740 AC: 3 AN: 40536

American (AMR) AF: 0.00 AC: 0 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4688

European-Finnish (FIN) AF: 0.000670 AC: 7 AN: 10454

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

European-Non Finnish (NFE) AF: 0.000782 AC: 53 AN: 67738

Other (OTH) AF: 0.000486 AC: 1 AN: 2058

Alfa AF: 0.000475 Hom.: 0

Bravo AF: 0.000340

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000400 AC: 3

ExAC AF: 0.000753 AC: 89

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	0.092
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.69
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.14
Sift	Benign	0.095	T
Sift4G	Benign	0.098	T
Polyphen		0.053	B
Vest4		0.11
MVP		0.29
MPC		2.0
ClinPred		0.029	T
GERP RS		2.7
Varity_R		0.027
gMVP		0.46
Mutation Taster		=97/3	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: rs201958681; hg19: chr3-125695953;