NM_001308313.2:c.70G>A

Variant names:

• chr3-125972124-G-A
• NM_001308313.2:c.70G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001308313.2(ROPN1B):​c.70G>A​(p.Ala24Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ROPN1B NM_001308313.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.70G>A	p.Ala24Thr	missense	Exon 3 of 7	NP_001295242.1	A0A140VKG6
	ROPN1B	NM_001012337.3		c.70G>A	p.Ala24Thr	missense	Exon 2 of 6	NP_001012337.1	A0A140VKG6
	ALG1L1P	NR_171196.1		n.116+18298C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROPN1B	ENST00000514116.6	TSL:1 MANE Select	c.70G>A	p.Ala24Thr	missense	Exon 3 of 7	ENSP00000426271.1	Q9BZX4-1
	ROPN1B	ENST00000251776.8	TSL:1	c.70G>A	p.Ala24Thr	missense	Exon 2 of 6	ENSP00000251776.4	Q9BZX4-1
	ROPN1B	ENST00000504401.1	TSL:1	c.70G>A	p.Ala24Thr	missense	Exon 2 of 2	ENSP00000424457.1	D6RAA3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	0.20
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.053
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.016	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.6
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.013	D
Polyphen		0.59	P
Vest4		0.51
MutPred		0.34		Gain of methylation at K19 (P = 0.0694)
MVP		0.90
MPC		0.44
ClinPred		0.96	D
GERP RS		3.4
Varity_R		0.35
gMVP		0.46
Mutation Taster		=90/10	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

hg19: chr3-125690967;