Genetic Variant FAM114A2:p.Ala330Val (chr5-154011245-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018691.4(FAM114A2):c.989C>T(p.Ala330Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM114A2
NM_018691.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

Publications

1 publications found

Variant links:

Genes affected

FAM114A2 (HGNC:1333): (family with sequence similarity 114 member A2)

FAM114A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07049543).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018691.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM114A2	NM_018691.4	MANE Select	c.989C>T	p.Ala330Val	missense	Exon 9 of 14	NP_061161.2	A0A140VKG4
FAM114A2	NM_001317993.2		c.989C>T	p.Ala330Val	missense	Exon 10 of 15	NP_001304922.1	Q9NRY5
FAM114A2	NM_001317994.2		c.989C>T	p.Ala330Val	missense	Exon 9 of 14	NP_001304923.1	A0A140VKG4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM114A2	ENST00000351797.9	TSL:1 MANE Select	c.989C>T	p.Ala330Val	missense	Exon 9 of 14	ENSP00000341597.4	Q9NRY5
FAM114A2	ENST00000520667.5	TSL:1	c.989C>T	p.Ala330Val	missense	Exon 10 of 15	ENSP00000430384.1	Q9NRY5
FAM114A2	ENST00000522858.5	TSL:1	c.989C>T	p.Ala330Val	missense	Exon 9 of 14	ENSP00000430489.1	Q9NRY5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722572

African (AFR)

AF:

0.00

AC:

AN:

33250

American (AMR)

AF:

0.00

AC:

AN:

44284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26000

East Asian (EAS)

AF:

0.00

AC:

AN:

39468

South Asian (SAS)

AF:

0.00

AC:

AN:

85216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104502

Other (OTH)

AF:

0.00

AC:

AN:

60078

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.010

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.70

M_CAP

Benign

0.0032

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

2.3

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.71

REVEL

Benign

0.017

Sift

Benign

0.53

Sift4G

Benign

0.73

Polyphen

0.0010

Vest4

0.24

MutPred

0.26

Loss of ubiquitination at K325 (P = 0.0777)

MVP

0.092

MPC

0.021

ClinPred

0.33

GERP RS

2.8

Varity_R

0.035

gMVP

0.083

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over