rs775431185

Variant names:

• chr5-10461197-C-A
• NM_031916.5:c.431C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-10461197-C-A
• chr5-10461197-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031916.5(ROPN1L):​c.431C>A​(p.Ala144Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. A144V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ROPN1L NM_031916.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63

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]

LOC124900940 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROPN1L	NM_031916.5	c.431C>A	p.Ala144Glu	missense_variant	Exon 4 of 5	ENST00000274134.5	NP_114122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROPN1L	ENST00000274134.5	c.431C>A	p.Ala144Glu	missense_variant	Exon 4 of 5	1	NM_031916.5	ENSP00000274134.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461260 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726936

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.0097	T
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.99	D;D
Vest4		0.78
MutPred		0.46		Gain of disorder (P = 0.0481);Gain of disorder (P = 0.0481);
MVP		0.41
MPC		0.75
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.40
gMVP		0.76

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-10461309;