5-153993102-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018691.4(FAM114A2):​c.1392C>G​(p.Asn464Lys) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

FAM114A2
NM_018691.4 missense

Scores

5
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.853
Variant links:
Genes affected
FAM114A2 (HGNC:1333): (family with sequence similarity 114 member A2)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM114A2NM_018691.4 linkc.1392C>G p.Asn464Lys missense_variant Exon 14 of 14 ENST00000351797.9 NP_061161.2 Q9NRY5A0A140VKG4I6L9D5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM114A2ENST00000351797.9 linkc.1392C>G p.Asn464Lys missense_variant Exon 14 of 14 1 NM_018691.4 ENSP00000341597.4 Q9NRY5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 25, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1392C>G (p.N464K) alteration is located in exon 14 (coding exon 13) of the FAM114A2 gene. This alteration results from a C to G substitution at nucleotide position 1392, causing the asparagine (N) at amino acid position 464 to be replaced by a lysine (K). 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
Pathogenic
0.80
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
D;D;D;T
Eigen
Benign
0.15
Eigen_PC
Benign
0.021
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.93
.;.;D;D
M_CAP
Benign
0.031
D
MetaRNN
Pathogenic
0.75
D;D;D;D
MetaSVM
Benign
-0.87
T
MutationAssessor
Pathogenic
2.9
M;M;M;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-5.2
D;D;D;D
REVEL
Benign
0.28
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.0050
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.80
MutPred
0.63
Gain of ubiquitination at N464 (P = 0.0203);Gain of ubiquitination at N464 (P = 0.0203);Gain of ubiquitination at N464 (P = 0.0203);.;
MVP
0.20
MPC
0.18
ClinPred
1.0
D
GERP RS
-2.1
Varity_R
0.87
gMVP
0.81

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: chr5-153372662; API