Variant 12-13055794-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020853.2(FAM234B):c.281C>A(p.Ala94Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,614,176 control chromosomes in the GnomAD database, including 17 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 0.0060 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 10 hom. )

Consequence

FAM234B
NM_020853.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.44

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=0.0042138696).

BP6

Variant 12-13055794-C-A is Benign according to our data. Variant chr12-13055794-C-A is described in ClinVar as [Benign]. Clinvar id is 3055457.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00603 (919/152306) while in subpopulation AFR AF= 0.021 (872/41564). AF 95% confidence interval is 0.0198. There are 7 homozygotes in gnomad4. There are 442 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM234B	NM_020853.2 linkuse as main transcript	c.281C>A	p.Ala94Glu	missense_variant	2/13	ENST00000197268.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM234B	ENST00000197268.13 linkuse as main transcript	c.281C>A	p.Ala94Glu	missense_variant	2/13	1	NM_020853.2	P1
FAM234B	ENST00000416494.6 linkuse as main transcript	c.281C>A	p.Ala94Glu	missense_variant, NMD_transcript_variant	2/14	2

Frequencies

GnomAD3 genomes

AF:

0.00592

AC:

901

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00162

AC:

406

AN:

250942

Hom.:

AF XY:

0.00114

AC XY:

155

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.000868

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:

0.0000529

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000616

AC:

900

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

384

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0219

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00603

AC:

919

AN:

152306

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

442

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0210

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000848

Hom.:

Bravo

AF:

0.00726

ESP6500AA

AF:

0.0229

AC:

101

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00206

AC:

250

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Apr 25, 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

0.13

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Benign

0.17

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.93

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.2

REVEL

Benign

0.045

Sift

Benign

0.037

Sift4G

Benign

0.18

Polyphen

0.72

Vest4

0.40

MVP

0.29

MPC

0.50

ClinPred

0.033

GERP RS

4.4

Varity_R

0.14

gMVP

0.30

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