18-13682058-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152352.4(FAM210A):​c.20G>A​(p.Arg7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000812 in 1,600,014 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

FAM210A
NM_152352.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.412
Variant links:
Genes affected
FAM210A (HGNC:28346): (family with sequence similarity 210 member A) Predicted to be located in cytoplasm. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09099448).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM210ANM_152352.4 linkc.20G>A p.Arg7Gln missense_variant Exon 2 of 4 ENST00000651643.1 NP_689565.2 Q96ND0
FAM210ANM_001098801.2 linkc.20G>A p.Arg7Gln missense_variant Exon 3 of 5 NP_001092271.1 Q96ND0
FAM210AXM_024451083.2 linkc.20G>A p.Arg7Gln missense_variant Exon 2 of 4 XP_024306851.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM210AENST00000651643.1 linkc.20G>A p.Arg7Gln missense_variant Exon 2 of 4 NM_152352.4 ENSP00000498370.1 Q96ND0

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152096
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000833
AC:
2
AN:
240132
Hom.:
0
AF XY:
0.00000772
AC XY:
1
AN XY:
129538
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000358
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000916
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000760
AC:
11
AN:
1447918
Hom.:
0
Cov.:
30
AF XY:
0.00000974
AC XY:
7
AN XY:
718804
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000815
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152096
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.20G>A (p.R7Q) alteration is located in exon 3 (coding exon 1) of the FAM210A gene. This alteration results from a G to A substitution at nucleotide position 20, causing the arginine (R) at amino acid position 7 to be replaced by a glutamine (Q). 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
0.081
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
14
DANN
Benign
0.96
DEOGEN2
Benign
0.021
T;T;T;.
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.71
.;T;T;T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.091
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.6
L;L;.;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.50
N;N;.;.
REVEL
Benign
0.076
Sift
Uncertain
0.021
D;D;.;.
Sift4G
Benign
0.067
T;T;.;.
Polyphen
0.016
B;B;.;.
Vest4
0.19
MutPred
0.18
Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);
MVP
0.092
MPC
0.13
ClinPred
0.053
T
GERP RS
0.60
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.024
gMVP
0.15

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: rs745561931; hg19: chr18-13682057; COSMIC: COSV59183822; API