rs374469503

Variant summary

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

The NM_001014840.2(CUTA):​c.258G>T​(p.Arg86Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R86R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CUTA
NM_001014840.2 missense, splice_region

Scores

5
3
11
Splicing: ADA: 0.9952
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.94
Variant links:
Genes affected
CUTA (HGNC:21101): (cutA divalent cation tolerance homolog) Enables enzyme binding activity. Involved in protein localization. Located in membrane. [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, 0.818

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CUTANM_001014840.2 linkc.258G>T p.Arg86Ser missense_variant, splice_region_variant Exon 3 of 6 ENST00000488034.6 NP_001014840.1 O60888-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CUTAENST00000488034.6 linkc.258G>T p.Arg86Ser missense_variant, splice_region_variant Exon 3 of 6 2 NM_001014840.2 ENSP00000417544.1 O60888-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251452
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135906
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461892
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Pathogenic
0.24
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
.;.;T;.;T;.;.;.
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.064
FATHMM_MKL
Benign
0.59
D
LIST_S2
Pathogenic
0.98
D;D;D;.;D;D;.;.
M_CAP
Benign
0.022
T
MetaRNN
Pathogenic
0.82
D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.3
.;.;M;.;.;.;.;.
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-3.5
D;.;D;.;D;D;D;D
REVEL
Benign
0.27
Sift
Benign
0.065
T;.;T;.;T;T;T;T
Sift4G
Benign
0.16
T;T;T;T;T;T;T;T
Polyphen
0.12
B;.;B;.;.;.;.;.
Vest4
0.77
MutPred
0.66
.;.;Loss of MoRF binding (P = 0.0269);.;.;Loss of MoRF binding (P = 0.0269);.;.;
MVP
0.57
MPC
0.33
ClinPred
0.83
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.87
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.90
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs374469503; hg19: chr6-33385087; API