X-71592146-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_052957.5(GCNA):​c.84C>G​(p.Ser28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 20)
Exomes 𝑓: 0.000029 ( 0 hom. 8 hem. )
Failed GnomAD Quality Control

Consequence

GCNA
NM_052957.5 missense

Scores

1
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0640
Variant links:
Genes affected
GCNA (HGNC:15805): (germ cell nuclear acidic peptidase) 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 Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.042909354).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GCNANM_052957.5 linkc.84C>G p.Ser28Arg missense_variant Exon 3 of 13 ENST00000373696.8 NP_443189.1 Q96QF7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GCNAENST00000373696.8 linkc.84C>G p.Ser28Arg missense_variant Exon 3 of 13 1 NM_052957.5 ENSP00000362800.3 Q96QF7
GCNAENST00000373695.1 linkc.84C>G p.Ser28Arg missense_variant Exon 2 of 12 1 ENSP00000362799.1 Q96QF7

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
4
AN:
111148
Hom.:
0
Cov.:
20
AF XY:
0.00
AC XY:
0
AN XY:
33336
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000971
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:
0.0000565
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000274
AC:
5
AN:
182453
Hom.:
0
AF XY:
0.0000448
AC XY:
3
AN XY:
66929
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000725
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000490
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000293
AC:
32
AN:
1093114
Hom.:
0
Cov.:
28
AF XY:
0.0000223
AC XY:
8
AN XY:
359012
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000285
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000166
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000247
Gnomad4 NFE exome
AF:
0.0000286
Gnomad4 OTH exome
AF:
0.0000218
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000360
AC:
4
AN:
111148
Hom.:
0
Cov.:
20
AF XY:
0.00
AC XY:
0
AN XY:
33336
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000971
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000565
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000136
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.84C>G (p.S28R) alteration is located in exon 3 (coding exon 2) of the ACRC gene. This alteration results from a C to G substitution at nucleotide position 84, causing the serine (S) at amino acid position 28 to be replaced by an arginine (R). 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
0.47
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
1.4
DANN
Benign
0.85
DEOGEN2
Benign
0.0089
T;T
FATHMM_MKL
Benign
0.062
N
LIST_S2
Benign
0.34
.;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.043
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.38
N;N
REVEL
Benign
0.013
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.57
T;T
Polyphen
0.0060
B;B
Vest4
0.16
MutPred
0.21
Loss of phosphorylation at S28 (P = 0.0283);Loss of phosphorylation at S28 (P = 0.0283);
MVP
0.043
MPC
0.65
ClinPred
0.11
T
GERP RS
0.23
Varity_R
0.17
gMVP
0.045

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs35103538; hg19: chrX-70811996; API