20-845432-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001042353.3(FAM110A):​c.628G>T​(p.Gly210Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

FAM110A
NM_001042353.3 missense

Scores

14
3
2

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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.92

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM110ANM_001042353.3 linkc.628G>T p.Gly210Cys 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.628G>T p.Gly210Cys missense_variant 2/21 NM_001042353.3 ENSP00000371367.3 Q9BQ89

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
33

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 GeneticsSep 11, 2024The c.628G>T (p.G210C) alteration is located in exon 2 (coding exon 1) of the FAM110A gene. This alteration results from a G to T substitution at nucleotide position 628, causing the glycine (G) at amino acid position 210 to be replaced by a cysteine (C). 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
0.94
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.39
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.42
T;T;T;T;T
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
.;.;.;.;D
M_CAP
Pathogenic
0.35
D
MetaRNN
Pathogenic
0.92
D;D;D;D;D
MetaSVM
Uncertain
0.44
D
MutationAssessor
Pathogenic
3.3
M;M;M;M;M
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-9.0
D;D;D;D;D
REVEL
Pathogenic
0.84
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
1.0
D;D;D;D;D
Vest4
0.95
MutPred
0.70
Loss of disorder (P = 0.1105);Loss of disorder (P = 0.1105);Loss of disorder (P = 0.1105);Loss of disorder (P = 0.1105);Loss of disorder (P = 0.1105);
MVP
0.94
MPC
1.9
ClinPred
1.0
D
GERP RS
4.6
Varity_R
0.92
gMVP
0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-826075; API