17-76081645-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_180990.4(ZACN):ā€‹c.770G>Cā€‹(p.Arg257Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

ZACN
NM_180990.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.70
Variant links:
Genes affected
ZACN (HGNC:29504): (zinc activated ion channel) LGICZ1 is a zinc-activated ligand-gated ion channel that defines a new subgroup of the cysteine-loop superfamily of ligand-gated ion channels (Davies et al., 2003 [PubMed 12381728]).[supplied by OMIM, Mar 2008]
EXOC7 (HGNC:23214): (exocyst complex component 7) The protein encoded by this gene is a component of the exocyst complex. The exocyst complex plays a critical role in vesicular trafficking and the secretory pathway by targeting post-Golgi vesicles to the plasma membrane. The encoded protein is required for assembly of the exocyst complex and docking of the complex to the plasma membrane. The encoded protein may also play a role in pre-mRNA splicing through interactions with pre-mRNA-processing factor 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Nov 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11308992).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZACNNM_180990.4 linkc.770G>C p.Arg257Pro missense_variant Exon 7 of 9 ENST00000334586.10 NP_851321.2 Q401N2-1
EXOC7NM_001013839.4 linkc.*2003C>G 3_prime_UTR_variant Exon 19 of 19 ENST00000589210.6 NP_001013861.1 Q9UPT5-1Q63HP7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZACNENST00000334586.10 linkc.770G>C p.Arg257Pro missense_variant Exon 7 of 9 1 NM_180990.4 ENSP00000334854.5 Q401N2-1
EXOC7ENST00000589210 linkc.*2003C>G 3_prime_UTR_variant Exon 19 of 19 1 NM_001013839.4 ENSP00000468404.1 Q9UPT5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461780
Hom.:
0
Cov.:
35
AF XY:
0.00000275
AC XY:
2
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
0.18
DANN
Benign
0.83
DEOGEN2
Benign
0.0029
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.39
T
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.52
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-2.0
N
REVEL
Uncertain
0.38
Sift
Benign
0.071
T
Sift4G
Uncertain
0.056
T
Polyphen
0.63
P
Vest4
0.24
MutPred
0.49
Loss of solvent accessibility (P = 0.1473);
MVP
0.14
MPC
0.20
ClinPred
0.35
T
GERP RS
-9.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.30
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs776661652; hg19: chr17-74077726; API