Variant 12-13058537-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020853.2(FAM234B):c.520G>A(p.Gly174Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,612,618 control chromosomes in the GnomAD database, including 499 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 37 hom., cov: 32)

Exomes 𝑓: 0.020 ( 462 hom. )

Consequence

FAM234B
NM_020853.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

FAM234B (HGNC:29288): (family with sequence similarity 234 member B) Predicted to be located in Golgi apparatus and cytoskeleton. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM234B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038429499).

BP6

Variant 12-13058537-G-A is Benign according to our data. Variant chr12-13058537-G-A is described in ClinVar as [Benign]. Clinvar id is 3039313.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM234B	NM_020853.2 linkuse as main transcript	c.520G>A	p.Gly174Arg	missense_variant	3/13	ENST00000197268.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM234B	ENST00000197268.13 linkuse as main transcript	c.520G>A	p.Gly174Arg	missense_variant	3/13	1	NM_020853.2	P1
FAM234B	ENST00000416494.6 linkuse as main transcript	c.520G>A	p.Gly174Arg	missense_variant, NMD_transcript_variant	3/14	2

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2205

AN:

150930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00502

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.0597

Gnomad SAS

AF:

0.0480

Gnomad FIN

AF:

0.00466

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0178

Gnomad OTH

AF:

0.0183

GnomAD3 exomes

AF:

0.0210

AC:

5288

AN:

251428

Hom.:

107

AF XY:

0.0229

AC XY:

3113

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00461

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.0301

Gnomad EAS exome

AF:

0.0495

Gnomad SAS exome

AF:

0.0495

Gnomad FIN exome

AF:

0.00554

Gnomad NFE exome

AF:

0.0183

Gnomad OTH exome

AF:

0.0189

GnomAD4 exome

AF:

0.0199

AC:

29124

AN:

1461570

Hom.:

462

Cov.:

AF XY:

0.0208

AC XY:

15156

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00460

Gnomad4 AMR exome

AF:

0.00537

Gnomad4 ASJ exome

AF:

0.0303

Gnomad4 EAS exome

AF:

0.0653

Gnomad4 SAS exome

AF:

0.0465

Gnomad4 FIN exome

AF:

0.00612

Gnomad4 NFE exome

AF:

0.0177

Gnomad4 OTH exome

AF:

0.0203

GnomAD4 genome

AF:

0.0147

AC:

2224

AN:

151048

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1104

AN XY:

73732

show subpopulations

Gnomad4 AFR

AF:

0.00490

Gnomad4 AMR

AF:

0.00501

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.0598

Gnomad4 SAS

AF:

0.0478

Gnomad4 FIN

AF:

0.00466

Gnomad4 NFE

AF:

0.0178

Gnomad4 OTH

AF:

0.0210

Alfa

AF:

0.0203

Hom.:

Bravo

AF:

0.0137

TwinsUK

AF:

0.0197

AC:

ALSPAC

AF:

0.0189

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0176

AC:

151

ExAC

AF:

0.0215

AC:

2605

Asia WGS

AF:

0.0520

AC:

181

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FAM234B-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.47

Cadd

Benign

9.8

Dann

Benign

0.64

DEOGEN2

Benign

0.0056

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.90

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.78

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.47

REVEL

Benign

0.11

Sift

Benign

0.55

Sift4G

Benign

0.15

Polyphen

0.93

Vest4

0.10

MutPred

0.48

Gain of MoRF binding (P = 0.0094);

MPC

0.16

ClinPred

0.017

GERP RS

4.0

Varity_R

0.031

gMVP

0.68

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