Genetic Variant FAM114A2:p.Glu307Ala (chr5-154011314-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018691.4(FAM114A2):c.920A>C(p.Glu307Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,459,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

FAM114A2
NM_018691.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.26

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM114A2	NM_018691.4 link	c.920A>C	p.Glu307Ala	missense_variant	Exon 9 of 14	ENST00000351797.9	NP_061161.2	Q9NRY5A0A140VKG4I6L9D5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM114A2	ENST00000351797.9 link	c.920A>C	p.Glu307Ala	missense_variant	Exon 9 of 14	1	NM_018691.4	ENSP00000341597.4	Q9NRY5
FAM114A2	ENST00000520667.5 link	c.920A>C	p.Glu307Ala	missense_variant	Exon 10 of 15	1		ENSP00000430384.1	Q9NRY5
FAM114A2	ENST00000522858.5 link	c.920A>C	p.Glu307Ala	missense_variant	Exon 9 of 14	1		ENSP00000430489.1	Q9NRY5
FAM114A2	ENST00000520313.5 link	c.710A>C	p.Glu237Ala	missense_variant	Exon 8 of 13	2		ENSP00000429088.1	E7ESJ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000804

AC:

AN:

248804

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134408

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459364

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725976

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.920A>C (p.E307A) alteration is located in exon 9 (coding exon 8) of the FAM114A2 gene. This alteration results from a A to C substitution at nucleotide position 920, causing the glutamic acid (E) at amino acid position 307 to be replaced by an alanine (A). 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

0.12

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T;T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.87

.;.;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.35

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

M;M;M;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-4.4

D;D;D;D

REVEL

Benign

0.12

Sift

Uncertain

0.013

D;D;D;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.98

D;D;D;P

Vest4

0.54

MutPred

0.11

Loss of methylation at K311 (P = 0.0533);Loss of methylation at K311 (P = 0.0533);Loss of methylation at K311 (P = 0.0533);.;

MVP

0.28

MPC

0.026

ClinPred

0.94

GERP RS

4.7

Varity_R

0.27

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.28

Position offset: 6

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