chr14-35081056-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_173607.5(FAM177A1):c.539A>G(p.Glu180Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Consequence
FAM177A1
NM_173607.5 missense
NM_173607.5 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 6.33
Genes affected
FAM177A1 (HGNC:19829): (family with sequence similarity 177 member A1) This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3365041).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAM177A1 | NM_173607.5 | c.539A>G | p.Glu180Gly | missense_variant | 5/5 | ENST00000280987.9 | |
FAM177A1 | NM_001079519.1 | c.470A>G | p.Glu157Gly | missense_variant | 7/7 | ||
FAM177A1 | NM_001289022.3 | c.470A>G | p.Glu157Gly | missense_variant | 6/6 | ||
LOC101927178 | NR_110415.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAM177A1 | ENST00000280987.9 | c.539A>G | p.Glu180Gly | missense_variant | 5/5 | 1 | NM_173607.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152092Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152092Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74310
GnomAD4 genome
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2023 | The c.539A>G (p.E180G) alteration is located in exon 5 (coding exon 5) of the FAM177A1 gene. This alteration results from a A to G substitution at nucleotide position 539, causing the glutamic acid (E) at amino acid position 180 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Benign
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;.
Vest4
MutPred
Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);.;.;
MVP
MPC
0.090
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at