chr4-1655009-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001174070.3(FAM53A):​c.851G>A​(p.Arg284His) variant causes a missense change. The variant allele was found at a frequency of 0.00000904 in 1,549,220 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R284C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

FAM53A
NM_001174070.3 missense

Scores

5
12
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60
Variant links:
Genes affected
FAM53A (HGNC:31860): (family with sequence similarity 53 member A) Predicted to be involved in protein import into nucleus. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM53ANM_001174070.3 linkc.851G>A p.Arg284His missense_variant Exon 4 of 5 ENST00000308132.11 NP_001167541.1 Q6NSI3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM53AENST00000308132.11 linkc.851G>A p.Arg284His missense_variant Exon 4 of 5 2 NM_001174070.3 ENSP00000310057.6 Q6NSI3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152250
Hom.:
0
Cov.:
33
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000787
AC:
11
AN:
1396970
Hom.:
0
Cov.:
30
AF XY:
0.0000131
AC XY:
9
AN XY:
689318
show subpopulations
Gnomad4 AFR exome
AF:
0.0000330
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000132
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000833
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152250
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74390
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000762
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.851G>A (p.R284H) alteration is located in exon 4 (coding exon 3) of the FAM53A gene. This alteration results from a G to A substitution at nucleotide position 851, causing the arginine (R) at amino acid position 284 to be replaced by a histidine (H). 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
0.53
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
23
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.36
T;.;T;T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D;.;.
M_CAP
Uncertain
0.23
D
MetaRNN
Uncertain
0.65
D;D;D;D
MetaSVM
Uncertain
-0.095
T
MutationAssessor
Pathogenic
3.3
M;.;M;M
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.9
D;D;D;D
REVEL
Uncertain
0.50
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.76
MVP
0.65
MPC
0.53
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.67
gMVP
0.18

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: rs1252047894; hg19: chr4-1656736; COSMIC: COSV100356938; COSMIC: COSV100356938; API