chr4-1641465-C-A

Variant summary

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

The NM_001174070.3(FAM53A):​c.1025G>T​(p.Gly342Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FAM53A
NM_001174070.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.825
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]

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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=0.049172044).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM53ANM_001174070.3 linkc.1025G>T p.Gly342Val missense_variant Exon 5 of 5 ENST00000308132.11 NP_001167541.1 Q6NSI3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM53AENST00000308132.11 linkc.1025G>T p.Gly342Val missense_variant Exon 5 of 5 2 NM_001174070.3 ENSP00000310057.6 Q6NSI3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 30, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1025G>T (p.G342V) alteration is located in exon 5 (coding exon 4) of the FAM53A gene. This alteration results from a G to T substitution at nucleotide position 1025, causing the glycine (G) at amino acid position 342 to be replaced by a valine (V). 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
0.079
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.55
DANN
Benign
0.25
DEOGEN2
Benign
0.0038
T;T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.44
T;.;.
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.049
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L;L;L
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.21
N;N;N
REVEL
Benign
0.028
Sift
Benign
0.36
T;T;T
Sift4G
Benign
0.63
T;T;T
Polyphen
0.10
B;B;B
Vest4
0.040
MutPred
0.17
Gain of glycosylation at T345 (P = 0.0122);Gain of glycosylation at T345 (P = 0.0122);Gain of glycosylation at T345 (P = 0.0122);
MVP
0.12
MPC
0.46
ClinPred
0.12
T
GERP RS
-2.4
Varity_R
0.041
gMVP
0.040

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-1643192; API