Genetic Variant NM_018691.4:c.1127C>T (chr5-154002380-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_018691.4(FAM114A2):c.1127C>T(p.Ala376Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,613,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

FAM114A2
NM_018691.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.27

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25735378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM114A2	NM_018691.4 link	c.1127C>T	p.Ala376Val	missense_variant	Exon 11 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.1127C>T	p.Ala376Val	missense_variant	Exon 11 of 14	1	NM_018691.4	ENSP00000341597.4	Q9NRY5
FAM114A2	ENST00000520667.5 link	c.1127C>T	p.Ala376Val	missense_variant	Exon 12 of 15	1		ENSP00000430384.1	Q9NRY5
FAM114A2	ENST00000522858.5 link	c.1127C>T	p.Ala376Val	missense_variant	Exon 11 of 14	1		ENSP00000430489.1	Q9NRY5
FAM114A2	ENST00000520313.5 link	c.917C>T	p.Ala306Val	missense_variant	Exon 10 of 13	2		ENSP00000429088.1	E7ESJ7

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250484

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135320

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461438

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000577

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1127C>T (p.A376V) alteration is located in exon 11 (coding exon 10) of the FAM114A2 gene. This alteration results from a C to T substitution at nucleotide position 1127, causing the alanine (A) at amino acid position 376 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

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

T;T;T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.78

.;.;T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;M;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.55

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.37

T;T;T;T

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.99

D;D;D;D

Vest4

0.60

MutPred

0.34

Loss of disorder (P = 0.0983);Loss of disorder (P = 0.0983);Loss of disorder (P = 0.0983);.;

MVP

0.13

MPC

0.054

ClinPred

0.13

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.073

gMVP

0.26

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