chr6-33418157-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000374500.10(CUTA):​c.-98G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

CUTA
ENST00000374500.10 5_prime_UTR

Scores

1
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.145
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]
SYNGAP1 (HGNC:11497): (synaptic Ras GTPase activating protein 1) This gene encodes a Ras GTPase activating protein that is a member of the N-methyl-D-aspartate receptor complex. The N-terminal domain of the protein contains a Ras-GAP domain, a pleckstrin homology domain, and a C2 domain that may be involved in binding of calcium and phospholipids. The C-terminal domain consists of a ten histidine repeat region, serine and tyrosine phosphorylation sites, and a T/SXV motif required for postsynaptic scaffold protein interaction. The encoded protein negatively regulates Ras, Rap and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking to the postsynaptic membrane to regulate synaptic plasticity and neuronal homeostasis. Allelic variants of this gene are associated with intellectual disability and autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.022693038).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CUTANM_001014840.2 linkc.-157G>A upstream_gene_variant ENST00000488034.6 NP_001014840.1 O60888-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CUTAENST00000488034.6 linkc.-157G>A upstream_gene_variant 2 NM_001014840.2 ENSP00000417544.1 O60888-1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152240
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000112
AC:
28
AN:
251042
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135736
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.000550
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000529
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1461828
Hom.:
0
Cov.:
33
AF XY:
0.0000316
AC XY:
23
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000447
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:
0.0000234
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000656
AC:
10
AN:
152358
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000793
ExAC
AF:
0.000115
AC:
14
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.29G>A (p.G10E) alteration is located in exon 1 (coding exon 1) of the CUTA gene. This alteration results from a G to A substitution at nucleotide position 29, causing the glycine (G) at amino acid position 10 to be replaced by a glutamic acid (E). 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
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
11
DANN
Benign
0.96
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.32
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.023
T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.11
N
REVEL
Benign
0.091
Sift
Uncertain
0.023
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.010
B
Vest4
0.27
MVP
0.13
MPC
0.31
ClinPred
0.46
T
GERP RS
2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
gMVP
0.42

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

LitVar

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

Other links and lift over

dbSNP: rs200627064; hg19: chr6-33385934; API