dbSNP rs143483187: FAM13B:p.Tyr619Cys (chr5-137952702-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP3BP4

The NM_001385994.1(FAM13B):c.1856A>G(p.Tyr619Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000713 in 1,599,206 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 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

FAM13B
NM_001385994.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38

Publications

0 publications found

Variant links:

Genes affected

FAM13B (HGNC:1335): (family with sequence similarity 13 member B) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

FAM13B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 6: BayesDel_addAF, BayesDel_noAF, Cadd, Eigen, FATHMM_MKL, PROVEAN [when max_spliceai, MetaRNN, MutationAssessor, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.41813508).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385994.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM13B	NM_001385994.1	MANE Select	c.1856A>G	p.Tyr619Cys	missense	Exon 17 of 24	NP_001372923.1	A0A8I5KSB9
FAM13B	NM_001385921.1		c.1790A>G	p.Tyr597Cys	missense	Exon 17 of 24	NP_001372850.1	A0A2X0SG06
FAM13B	NM_016603.4		c.1790A>G	p.Tyr597Cys	missense	Exon 16 of 23	NP_057687.2	A0A2X0SG06

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM13B	ENST00000689681.1	MANE Select	c.1856A>G	p.Tyr619Cys	missense	Exon 17 of 24	ENSP00000509788.1	A0A8I5KSB9
FAM13B	ENST00000033079.7	TSL:1	c.1790A>G	p.Tyr597Cys	missense	Exon 16 of 23	ENSP00000033079.3	Q9NYF5-1
FAM13B	ENST00000420893.6	TSL:1	c.1790A>G	p.Tyr597Cys	missense	Exon 16 of 22	ENSP00000388521.2	Q9NYF5-2

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000451

AC:

AN:

244040

AF XY:

0.0000379

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000804

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000726

AC:

105

AN:

1447002

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

719456

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33074

American (AMR)

AF:

0.0000465

AC:

AN:

42972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25768

East Asian (EAS)

AF:

0.00

AC:

AN:

39452

South Asian (SAS)

AF:

0.00

AC:

AN:

83168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000896

AC:

AN:

1104852

Other (OTH)

AF:

0.0000502

AC:

AN:

59788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

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:

0.0000591

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000849

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000494

AC:

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

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.42

MetaSVM

Pathogenic

1.0

MutationAssessor

Benign

1.8

PhyloP100

5.4

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.58

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.46

MVP

0.75

MPC

0.14

ClinPred

0.26

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.19

Mutation Taster

=46/54

disease causing

(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