Genetic Variant FAM43B:p.Glu272Asp (chr1-20553789-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207334.3(FAM43B):c.816G>C(p.Glu272Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,475,688 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 1 hom. )

Consequence

FAM43B
NM_207334.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.273

Publications

0 publications found

Variant links:

Genes affected

FAM43B (HGNC:31791): (family with sequence similarity 43 member B)

FAM43B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005791813).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207334.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM43B	NM_207334.3	MANE Select	c.816G>C	p.Glu272Asp	missense	Exon 1 of 1	NP_997217.1	Q6ZT52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM43B	ENST00000332947.6	TSL:6 MANE Select	c.816G>C	p.Glu272Asp	missense	Exon 1 of 1	ENSP00000331397.4	Q6ZT52

Frequencies

GnomAD3 genomes

AF:

0.000616

AC:

AN:

150962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000461

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000141

AC:

AN:

98968

AF XY:

0.000109

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000305

Gnomad OTH exome

AF:

0.000725

GnomAD4 exome

AF:

0.0000664

AC:

AN:

1324618

Hom.:

Cov.:

AF XY:

0.0000597

AC XY:

AN XY:

653370

show subpopulations

African (AFR)

AF:

0.00191

AC:

AN:

26662

American (AMR)

AF:

0.000306

AC:

AN:

29418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22662

East Asian (EAS)

AF:

0.00

AC:

AN:

27704

South Asian (SAS)

AF:

0.0000404

AC:

AN:

74200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45466

Middle Eastern (MID)

AF:

0.000505

AC:

AN:

3962

European-Non Finnish (NFE)

AF:

0.00000288

AC:

AN:

1040690

Other (OTH)

AF:

0.000371

AC:

AN:

53854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000622

AC:

AN:

151070

Hom.:

Cov.:

AF XY:

0.000664

AC XY:

AN XY:

73824

show subpopulations

African (AFR)

AF:

0.00210

AC:

AN:

41448

American (AMR)

AF:

0.000461

AC:

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67568

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000641

Hom.:

Bravo

AF:

0.000699

ESP6500AA

AF:

0.00181

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000128

AC:

Asia WGS

AF:

0.000310

AC:

AN:

3240

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.7

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.022

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.26

M_CAP

Benign

0.062

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

PhyloP100

0.27

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.1

REVEL

Benign

0.065

Sift

Benign

0.10

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.10

MutPred

0.11

Loss of helix (P = 0.028)

MVP

0.12

ClinPred

0.0031

GERP RS

0.39

Varity_R

0.080

gMVP

0.089

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over