chr12-8222142-C-T

Variant summary

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

The NM_018088.3(FAM90A1):​c.1075G>A​(p.Gly359Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,611,932 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

FAM90A1
NM_018088.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.420
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 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=0.036559522).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM90A1NM_018088.3 linkc.1075G>A p.Gly359Ser 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.1075G>A p.Gly359Ser missense_variant Exon 7 of 7 1 NM_018088.3 ENSP00000445418.1 Q86YD7
FAM90A1ENST00000307435.10 linkc.1075G>A p.Gly359Ser missense_variant Exon 6 of 6 2 ENSP00000307798.6 Q86YD7

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152050
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000199
AC:
29
AN:
1459882
Hom.:
0
Cov.:
31
AF XY:
0.0000220
AC XY:
16
AN XY:
726246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152050
Hom.:
0
Cov.:
34
AF XY:
0.0000135
AC XY:
1
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
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
Alfa
AF:
0.0000664
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1075G>A (p.G359S) 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 1075, causing the glycine (G) at amino acid position 359 to be replaced by a serine (S). 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
0.068
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.36
DANN
Benign
0.62
DEOGEN2
Benign
0.00035
T;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.00032
N
LIST_S2
Benign
0.27
.;T
M_CAP
Benign
0.00067
T
MetaRNN
Benign
0.037
T;T
MetaSVM
Benign
-0.94
T
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
1.3
N;N
REVEL
Benign
0.0060
Sift
Benign
0.30
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0030
B;B
Vest4
0.024
MVP
0.048
MPC
0.29
ClinPred
0.023
T
GERP RS
-2.0
Varity_R
0.035
gMVP
0.046

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: rs745618696; hg19: chr12-8374738; API