17-9918059-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_201433.2(GAS7):​c.1259G>A​(p.Arg420Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,860 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 0.000079 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

GAS7
NM_201433.2 missense

Scores

4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00
Variant links:
Genes affected
GAS7 (HGNC:4169): (growth arrest specific 7) Growth arrest-specific 7 is expressed primarily in terminally differentiated brain cells and predominantly in mature cerebellar Purkinje neurons. GAS7 plays a putative role in neuronal development. Several transcript variants encoding proteins which vary in the N-terminus have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.21208355).
BS2
High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GAS7NM_201433.2 linkc.1259G>A p.Arg420Gln missense_variant Exon 13 of 14 ENST00000432992.7 NP_958839.1 O60861-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GAS7ENST00000432992.7 linkc.1259G>A p.Arg420Gln missense_variant Exon 13 of 14 1 NM_201433.2 ENSP00000407552.2 O60861-3

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152226
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000558
AC:
14
AN:
251058
Hom.:
0
AF XY:
0.0000590
AC XY:
8
AN XY:
135708
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461634
Hom.:
0
Cov.:
30
AF XY:
0.0000330
AC XY:
24
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152226
Hom.:
0
Cov.:
34
AF XY:
0.0000672
AC XY:
5
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000389
Hom.:
0
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000824
AC:
10

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1259G>A (p.R420Q) alteration is located in exon 13 (coding exon 13) of the GAS7 gene. This alteration results from a G to A substitution at nucleotide position 1259, causing the arginine (R) at amino acid position 420 to be replaced by a glutamine (Q). 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
Benign
0.12
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.078
.;.;T;.;.;.;T;.
Eigen
Benign
-0.068
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.92
.;.;D;D;D;.;D;D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.21
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
.;.;N;.;.;.;.;.
PrimateAI
Uncertain
0.68
T
REVEL
Benign
0.070
Sift4G
Benign
0.20
T;T;T;T;T;T;T;T
Polyphen
0.54, 0.024
.;.;P;.;B;.;.;.
Vest4
0.48
MVP
0.37
MPC
1.1
ClinPred
0.092
T
GERP RS
5.1
Varity_R
0.20
gMVP
0.85

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: rs200175032; hg19: chr17-9821376; COSMIC: COSV60436133; API