5-153994956-T-C

Variant summary

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

The NM_018691.4(FAM114A2):​c.1346A>G​(p.Asp449Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000329 in 1,609,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FAM114A2
NM_018691.4 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77
Variant links:
Genes affected
FAM114A2 (HGNC:1333): (family with sequence similarity 114 member A2)

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
FAM114A2NM_018691.4 linkc.1346A>G p.Asp449Gly missense_variant Exon 13 of 14 ENST00000351797.9 NP_061161.2 Q9NRY5A0A140VKG4I6L9D5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM114A2ENST00000351797.9 linkc.1346A>G p.Asp449Gly missense_variant Exon 13 of 14 1 NM_018691.4 ENSP00000341597.4 Q9NRY5

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152150
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000844
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251002
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135668
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000124
AC:
18
AN:
1457386
Hom.:
0
Cov.:
27
AF XY:
0.00000965
AC XY:
7
AN XY:
725348
show subpopulations
Gnomad4 AFR exome
AF:
0.000480
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152268
Hom.:
0
Cov.:
33
AF XY:
0.000175
AC XY:
13
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.000842
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000168
Hom.:
0
Bravo
AF:
0.000151
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 19, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1346A>G (p.D449G) alteration is located in exon 13 (coding exon 12) of the FAM114A2 gene. This alteration results from a A to G substitution at nucleotide position 1346, causing the aspartic acid (D) at amino acid position 449 to be replaced by a glycine (G). 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
0.16
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;T;T;T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.90
.;.;D;D
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.44
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.2
M;M;M;.
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-4.8
D;D;D;D
REVEL
Uncertain
0.32
Sift
Uncertain
0.012
D;D;D;D
Sift4G
Uncertain
0.0090
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.56
MVP
0.29
MPC
0.036
ClinPred
0.28
T
GERP RS
5.2
Varity_R
0.65
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs368648196; hg19: chr5-153374516; API