Genetic Variant NM_207334.3:c.775C>T (chr1-20553748-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_207334.3(FAM43B):c.775C>T(p.Arg259Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000954 in 1,468,262 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

FAM43B
NM_207334.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3557436).

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.775C>T	p.Arg259Cys	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.775C>T	p.Arg259Cys	missense	Exon 1 of 1	ENSP00000331397.4	Q6ZT52

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

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:

0.0000108

AC:

AN:

92564

AF XY:

0.0000193

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000387

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1317444

Hom.:

Cov.:

AF XY:

0.00000770

AC XY:

AN XY:

649592

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26452

American (AMR)

AF:

0.0000698

AC:

AN:

28640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22474

East Asian (EAS)

AF:

0.0000736

AC:

AN:

27190

South Asian (SAS)

AF:

0.0000135

AC:

AN:

73896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3880

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1038022

Other (OTH)

AF:

0.000131

AC:

AN:

53470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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:

0.0000133

AC:

AN:

150818

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73616

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41298

American (AMR)

AF:

0.00

AC:

AN:

15148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67508

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.0000113

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

Uncertain

0.51

BayesDel_addAF

Benign

0.0056

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Benign

0.16

Eigen_PC

Benign

0.065

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.0

PhyloP100

1.4

PrimateAI

Pathogenic

0.96

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.15

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.32

MutPred

0.28

Gain of catalytic residue at L260 (P = 0.0124)

MVP

0.31

ClinPred

0.99

GERP RS

3.5

Varity_R

0.56

gMVP

0.42

Mutation Taster

=76/24

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