5-154027280-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018691.4(FAM114A2):​c.685G>A​(p.Val229Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,613,312 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

FAM114A2
NM_018691.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.283
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.030861974).
BP6
Variant 5-154027280-C-T is Benign according to our data. Variant chr5-154027280-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2370392.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM114A2NM_018691.4 linkc.685G>A p.Val229Met missense_variant Exon 7 of 14 ENST00000351797.9 NP_061161.2 Q9NRY5A0A140VKG4I6L9D5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM114A2ENST00000351797.9 linkc.685G>A p.Val229Met missense_variant Exon 7 of 14 1 NM_018691.4 ENSP00000341597.4 Q9NRY5

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000758
AC:
19
AN:
250666
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135510
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000981
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000753
AC:
110
AN:
1461146
Hom.:
0
Cov.:
31
AF XY:
0.0000784
AC XY:
57
AN XY:
726890
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000846
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000614
Hom.:
0
Bravo
AF:
0.0000227
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000741
AC:
9
EpiCase
AF:
0.00
EpiControl
AF:
0.000237

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Nov 08, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
11
DANN
Benign
0.66
DEOGEN2
Benign
0.0050
T;T;T;T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.24
.;.;T;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.031
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.76
N;N;N;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
0.72
N;N;N;N
REVEL
Benign
0.0090
Sift
Benign
0.90
T;T;T;T
Sift4G
Benign
0.24
T;T;T;T
Polyphen
0.0060
B;B;B;B
Vest4
0.20
MutPred
0.33
Gain of disorder (P = 0.0769);Gain of disorder (P = 0.0769);Gain of disorder (P = 0.0769);.;
MVP
0.099
MPC
0.022
ClinPred
0.020
T
GERP RS
0.68
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.015
gMVP
0.061

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: rs371503130; hg19: chr5-153406840; COSMIC: COSV61078214; COSMIC: COSV61078214; API