20-845270-G-A

Variant summary

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

The NM_001042353.3(FAM110A):​c.466G>A​(p.Val156Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,494,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

FAM110A
NM_001042353.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35
Variant links:
Genes affected
FAM110A (HGNC:16188): (family with sequence similarity 110 member A) Predicted to be located in cytoplasm; microtubule organizing center; and spindle pole. [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=0.115876496).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM110ANM_001042353.3 linkc.466G>A p.Val156Ile missense_variant 2/2 ENST00000381941.8 NP_001035812.1 Q9BQ89

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM110AENST00000381941.8 linkc.466G>A p.Val156Ile missense_variant 2/21 NM_001042353.3 ENSP00000371367.3 Q9BQ89

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152010
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:
0.0000589
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000218
AC:
2
AN:
91558
Hom.:
0
AF XY:
0.0000200
AC XY:
1
AN XY:
49964
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000583
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
22
AN:
1342678
Hom.:
0
Cov.:
35
AF XY:
0.0000152
AC XY:
10
AN XY:
659506
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.0000208
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152010
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74262
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:
0.0000589
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

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 submitterclinical testingAmbry GeneticsNov 21, 2023The c.466G>A (p.V156I) alteration is located in exon 2 (coding exon 1) of the FAM110A gene. This alteration results from a G to A substitution at nucleotide position 466, causing the valine (V) at amino acid position 156 to be replaced by an isoleucine (I). 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
0.22
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.017
T;T;T;T;T
Eigen
Benign
0.020
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.80
.;.;.;.;T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.12
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M;M;M;M
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.43
N;N;N;N;N
REVEL
Benign
0.058
Sift
Benign
0.18
T;T;T;T;T
Sift4G
Benign
0.42
T;T;T;T;T
Polyphen
0.70
P;P;P;P;P
Vest4
0.044
MutPred
0.24
Gain of catalytic residue at P158 (P = 0.0309);Gain of catalytic residue at P158 (P = 0.0309);Gain of catalytic residue at P158 (P = 0.0309);Gain of catalytic residue at P158 (P = 0.0309);Gain of catalytic residue at P158 (P = 0.0309);
MVP
0.36
MPC
1.6
ClinPred
0.36
T
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.088
gMVP
0.39

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: rs1185775717; hg19: chr20-825913; API