Genetic Variant FAM114A2:p.Gln497Glu (chr5-153993005-G-C) – 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.1489C>G(p.Gln497Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,459,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

FAM114A2
NM_018691.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

Publications

1 publications found

Variant links:

Genes affected

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

FAM114A2 links:

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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=0.10191524).

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.1489C>G	p.Gln497Glu	missense	Exon 14 of 14	NP_061161.2	A0A140VKG4
FAM114A2	NM_001317993.2		c.1489C>G	p.Gln497Glu	missense	Exon 15 of 15	NP_001304922.1	Q9NRY5
FAM114A2	NM_001317994.2		c.1489C>G	p.Gln497Glu	missense	Exon 14 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.1489C>G	p.Gln497Glu	missense	Exon 14 of 14	ENSP00000341597.4	Q9NRY5
FAM114A2	ENST00000520667.5	TSL:1	c.1489C>G	p.Gln497Glu	missense	Exon 15 of 15	ENSP00000430384.1	Q9NRY5
FAM114A2	ENST00000522858.5	TSL:1	c.1489C>G	p.Gln497Glu	missense	Exon 14 of 14	ENSP00000430489.1	Q9NRY5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000240

AC:

AN:

250294

AF XY:

0.0000148

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459436

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726068

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.00

AC:

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.0000931

AC:

AN:

85924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110496

Other (OTH)

AF:

0.00

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

0.062

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.58

M_CAP

Benign

0.0050

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

PhyloP100

4.1

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.21

REVEL

Benign

0.16

Sift

Uncertain

0.023

Sift4G

Pathogenic

0.0

Polyphen

0.043

Vest4

0.14

MutPred

0.080

Loss of helix (P = 0.0376)

MVP

0.24

MPC

0.026

ClinPred

0.040

GERP RS

5.5

Varity_R

0.064

gMVP

0.30

Mutation Taster

=96/4

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over