Variant 12-13066671-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.884G>A(p.Arg295Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00677 in 1,613,616 control chromosomes in the GnomAD database, including 644 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.036 ( 328 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 316 hom. )

Consequence

FAM234B
NM_020853.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.13

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=0.002316624).

BP6

Variant 12-13066671-G-A is Benign according to our data. Variant chr12-13066671-G-A is described in ClinVar as [Benign]. Clinvar id is 3037880.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 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.884G>A	p.Arg295Gln	missense_variant	6/13	ENST00000197268.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAM234B	ENST00000197268.13 linkuse as main transcript	c.884G>A	p.Arg295Gln	missense_variant	6/13	1	NM_020853.2	P1
FAM234B	ENST00000537625.1 linkuse as main transcript	c.212G>A	p.Arg71Gln	missense_variant	3/9	1
FAM234B	ENST00000416494.6 linkuse as main transcript	c.884G>A	p.Arg295Gln	missense_variant, NMD_transcript_variant	6/14	2
FAM234B	ENST00000541950.1 linkuse as main transcript	n.221-1633G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0363

AC:

5520

AN:

152070

Hom.:

329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0278

GnomAD3 exomes

AF:

0.00964

AC:

2417

AN:

250764

Hom.:

137

AF XY:

0.00697

AC XY:

944

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.00708

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000491

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00370

AC:

5401

AN:

1461428

Hom.:

316

Cov.:

AF XY:

0.00315

AC XY:

2289

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.00774

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000192

Gnomad4 OTH exome

AF:

0.00843

GnomAD4 genome

AF:

0.0363

AC:

5524

AN:

152188

Hom.:

328

Cov.:

AF XY:

0.0348

AC XY:

2593

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.0185

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0275

Alfa

AF:

0.00722

Hom.:

Bravo

AF:

0.0415

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.125

AC:

551

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0117

AC:

1419

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000297

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

May 01, 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

0.069

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0077

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.035

FATHMM_MKL

Benign

0.65

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.55

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.19

N;N

REVEL

Benign

0.065

Sift

Benign

0.34

T;T

Sift4G

Benign

0.34

T;D

Polyphen

0.017

B;.

Vest4

0.090

MPC

0.30

ClinPred

0.014

GERP RS

3.5

Varity_R

0.022

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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