Variant 20-845193-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001042353.3(FAM110A):c.389C>T(p.Ala130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 1,562,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

FAM110A
NM_001042353.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0460

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]

FAM110A links:

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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=0.07061589).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM110A	NM_001042353.3 linkuse as main transcript	c.389C>T	p.Ala130Val	missense_variant	2/2	ENST00000381941.8	NP_001035812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM110A	ENST00000381941.8 linkuse as main transcript	c.389C>T	p.Ala130Val	missense_variant	2/2	1	NM_001042353.3	ENSP00000371367	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000142

AC:

AN:

1410492

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

698764

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000509

Gnomad4 ASJ exome

AF:

0.000245

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000101

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

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 submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.389C>T (p.A130V) alteration is located in exon 2 (coding exon 1) of the FAM110A gene. This alteration results from a C to T substitution at nucleotide position 389, causing the alanine (A) at amino acid position 130 to be replaced by a valine (V). 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

0.079

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;T;T;T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.66

.;.;.;.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.071

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;L;L;L

MutationTaster

Benign

0.98

N;N;N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.97

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.11

T;T;T;T;T

Sift4G

Benign

0.30

T;T;T;T;T

Polyphen

0.084

B;B;B;B;B

Vest4

0.011

MutPred

0.12

Loss of glycosylation at P127 (P = 0.1285);Loss of glycosylation at P127 (P = 0.1285);Loss of glycosylation at P127 (P = 0.1285);Loss of glycosylation at P127 (P = 0.1285);Loss of glycosylation at P127 (P = 0.1285);

MVP

0.19

MPC

0.75

ClinPred

0.14

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.054

gMVP

0.32

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over