8-84862313-G-T

Variant summary

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

The NM_173848.7(RALYL):​c.431G>T​(p.Gly144Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,434,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

RALYL
NM_173848.7 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.35
Variant links:
Genes affected
RALYL (HGNC:27036): (RALY RNA binding protein like) Enables identical protein binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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, 0.839

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RALYLNM_173848.7 linkuse as main transcriptc.431G>T p.Gly144Val missense_variant 6/9 ENST00000521268.6 NP_776247.3 Q86SE5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RALYLENST00000521268.6 linkuse as main transcriptc.431G>T p.Gly144Val missense_variant 6/91 NM_173848.7 ENSP00000430367.1 Q86SE5-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.97e-7
AC:
1
AN:
1434044
Hom.:
0
Cov.:
30
AF XY:
0.00000140
AC XY:
1
AN XY:
712828
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:
0.00
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 04, 2023The c.470G>T (p.G157V) alteration is located in exon 6 (coding exon 6) of the RALYL gene. This alteration results from a G to T substitution at nucleotide position 470, causing the glycine (G) at amino acid position 157 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Uncertain
0.076
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
31
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
T;T;T;.;.;.;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.96
.;.;D;D;D;D;D
M_CAP
Benign
0.022
T
MetaRNN
Pathogenic
0.84
D;D;D;D;D;D;D
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.3
M;M;M;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-3.0
D;D;D;D;D;D;D
REVEL
Benign
0.23
Sift
Uncertain
0.012
D;D;D;D;D;D;D
Sift4G
Uncertain
0.0090
D;D;D;D;D;D;D
Polyphen
0.99
D;D;D;D;.;D;.
Vest4
0.85
MutPred
0.60
Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);.;.;.;.;
MVP
0.58
MPC
0.042
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.46
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: chr8-85774548; API