chr5-10448283-G-A

Variant names:

• chr5-10448283-G-A
• rs375461849
• NM_031916.5:c.155G>A

Variant summary

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

The NM_031916.5(ROPN1L):​c.155G>A​(p.Gly52Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G52A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ROPN1L NM_031916.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.21
• Publications: 1 publications found

Genes affected

ROPN1L (HGNC:24060): (rhophilin associated tail protein 1 like) This gene encodes a member of the ropporin family. The encoded protein is present in sperm and interacts with A-kinase anchoring protein, AKAP3, through the amphipathic helix region of AKAP3. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2014]

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_031916.5. 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
	ROPN1L	NM_031916.5	MANE Select	c.155G>A	p.Gly52Glu	missense	Exon 2 of 5	NP_114122.2
	ROPN1L	NM_001201466.2		c.155G>A	p.Gly52Glu	missense	Exon 3 of 6	NP_001188395.1	Q96C74

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROPN1L	ENST00000274134.5	TSL:1 MANE Select	c.155G>A	p.Gly52Glu	missense	Exon 2 of 5	ENSP00000274134.4	Q96C74
	ROPN1L	ENST00000503804.5	TSL:2	c.155G>A	p.Gly52Glu	missense	Exon 3 of 6	ENSP00000421405.1	Q96C74
	ROPN1L	ENST00000510520.5	TSL:3	n.447G>A		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251472 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0089	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.26
Sift	Uncertain	0.020	D
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.74
MutPred		0.53		Loss of methylation at R51 (P = 0.0434)
MVP		0.51
MPC		0.85
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.68
gMVP		0.61
Mutation Taster		=25/75	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs375461849; hg19: chr5-10448395;