20-845411-G-C

Variant summary

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

The NM_001042353.3(FAM110A):ā€‹c.607G>Cā€‹(p.Glu203Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000075 ( 0 hom. )

Consequence

FAM110A
NM_001042353.3 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.98
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM110ANM_001042353.3 linkc.607G>C p.Glu203Gln 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.607G>C p.Glu203Gln missense_variant 2/21 NM_001042353.3 ENSP00000371367.3 Q9BQ89

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1461406
Hom.:
0
Cov.:
35
AF XY:
0.00000825
AC XY:
6
AN XY:
727024
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:
0.00000989
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

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 GeneticsJan 05, 2022The c.607G>C (p.E203Q) alteration is located in exon 2 (coding exon 1) of the FAM110A gene. This alteration results from a G to C substitution at nucleotide position 607, causing the glutamic acid (E) at amino acid position 203 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
Pathogenic
0.61
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;T;T;T;T
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
.;.;.;.;D
M_CAP
Benign
0.035
D
MetaRNN
Pathogenic
0.82
D;D;D;D;D
MetaSVM
Benign
-0.43
T
MutationAssessor
Uncertain
2.4
M;M;M;M;M
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-2.6
D;D;D;D;D
REVEL
Uncertain
0.45
Sift
Uncertain
0.0040
D;D;D;D;D
Sift4G
Uncertain
0.0090
D;D;D;D;D
Polyphen
1.0
D;D;D;D;D
Vest4
0.92
MVP
0.66
MPC
1.8
ClinPred
0.97
D
GERP RS
4.6
Varity_R
0.55
gMVP
0.69

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: rs201879889; hg19: chr20-826054; API