rs775431185

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

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

Scores

3
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.63
Variant links:
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]

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ACMG classification

Classification made for transcript

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
ROPN1LNM_031916.5 linkc.431C>A p.Ala144Glu missense_variant Exon 4 of 5 ENST00000274134.5 NP_114122.2 Q96C74

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ROPN1LENST00000274134.5 linkc.431C>A p.Ala144Glu missense_variant Exon 4 of 5 1 NM_031916.5 ENSP00000274134.4 Q96C74

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
show subpopulations
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; API