NM_018088.3:c.1307G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018088.3(FAM90A1):​c.1307G>C​(p.Gly436Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,596,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

FAM90A1
NM_018088.3 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0120
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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.02422306).
BP6
Variant 12-8221910-C-G is Benign according to our data. Variant chr12-8221910-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2223785.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM90A1NM_018088.3 linkc.1307G>C p.Gly436Ala 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.1307G>C p.Gly436Ala missense_variant Exon 7 of 7 1 NM_018088.3 ENSP00000445418.1 Q86YD7
FAM90A1ENST00000307435.10 linkc.1307G>C p.Gly436Ala missense_variant Exon 6 of 6 2 ENSP00000307798.6 Q86YD7

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152240
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000342
AC:
8
AN:
233984
Hom.:
0
AF XY:
0.0000233
AC XY:
3
AN XY:
128550
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000555
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000644
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000568
AC:
82
AN:
1444126
Hom.:
0
Cov.:
31
AF XY:
0.0000612
AC XY:
44
AN XY:
718804
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000702
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152240
Hom.:
0
Cov.:
34
AF XY:
0.0000403
AC XY:
3
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000426
AC:
5
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 01, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.65
DANN
Benign
0.51
DEOGEN2
Benign
0.0038
T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.00063
N
LIST_S2
Benign
0.41
.;T
M_CAP
Benign
0.00065
T
MetaRNN
Benign
0.024
T;T
MetaSVM
Benign
-0.93
T
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.031
Sift
Benign
1.0
T;T
Sift4G
Benign
0.78
T;T
Polyphen
0.0010
B;B
Vest4
0.053
MutPred
0.098
Loss of catalytic residue at G436 (P = 0.0799);Loss of catalytic residue at G436 (P = 0.0799);
MVP
0.067
MPC
0.32
ClinPred
0.021
T
GERP RS
0.060
Varity_R
0.035
gMVP
0.014

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: rs768616228; hg19: chr12-8374506; API