12-8222013-C-T

Variant summary

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

The NM_018088.3(FAM90A1):​c.1204G>A​(p.Gly402Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,599,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

FAM90A1
NM_018088.3 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.124
Variant links:
Genes affected
FAM90A1 (HGNC:25526): (family with sequence similarity 90 member A1) FAM90A1 belongs to subfamily I of the primate-specific FAM90A gene family, which originated from multiple duplications and rearrangements (Bosch et al., 2007 [PubMed 17684299]).[supplied by OMIM, Oct 2009]

Genome browser will be placed here

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=0.074796826).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM90A1NM_018088.3 linkc.1204G>A p.Gly402Arg missense_variant Exon 7 of 7 ENST00000538603.6 NP_060558.3 Q86YD7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM90A1ENST00000538603.6 linkc.1204G>A p.Gly402Arg missense_variant Exon 7 of 7 1 NM_018088.3 ENSP00000445418.1 Q86YD7
FAM90A1ENST00000307435.10 linkc.1204G>A p.Gly402Arg missense_variant Exon 6 of 6 2 ENSP00000307798.6 Q86YD7

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152206
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000295
AC:
7
AN:
237362
Hom.:
0
AF XY:
0.0000384
AC XY:
5
AN XY:
130316
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.000403
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000182
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000242
AC:
35
AN:
1447718
Hom.:
0
Cov.:
31
AF XY:
0.0000264
AC XY:
19
AN XY:
720582
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152206
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000167
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 29, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1204G>A (p.G402R) alteration is located in exon 7 (coding exon 4) of the FAM90A1 gene. This alteration results from a G to A substitution at nucleotide position 1204, causing the glycine (G) at amino acid position 402 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
Benign
0.22
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
14
DANN
Benign
0.82
DEOGEN2
Benign
0.073
T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0039
N
LIST_S2
Benign
0.38
.;T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.075
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Benign
0.013
Sift
Benign
0.031
D;D
Sift4G
Uncertain
0.041
D;D
Polyphen
0.27
B;B
Vest4
0.20
MutPred
0.29
Gain of MoRF binding (P = 0.0378);Gain of MoRF binding (P = 0.0378);
MVP
0.10
MPC
0.41
ClinPred
0.069
T
GERP RS
-1.1
Varity_R
0.092
gMVP
0.034

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: rs781068871; hg19: chr12-8374609; API