Genetic Variant FAM98B:p.Pro317Ser (chr15-38484306-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_173611.4(FAM98B):c.949C>T(p.Pro317Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,548,140 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 0.0000067 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

FAM98B
NM_173611.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

Publications

0 publications found

Variant links:

Genes affected

FAM98B (HGNC:26773): (family with sequence similarity 98 member B) Enables identical protein binding activity and protein methyltransferase activity. Involved in positive regulation of cell population proliferation; positive regulation of gene expression; and protein methylation. Located in cytoplasm and nucleoplasm. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

FAM98B links:

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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=0.37404165).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173611.4. 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
	FAM98B	NM_173611.4	MANE Select	c.949C>T	p.Pro317Ser	missense	Exon 8 of 8	NP_775882.2	Q52LJ0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM98B	ENST00000397609.6	TSL:5 MANE Select	c.949C>T	p.Pro317Ser	missense	Exon 8 of 8	ENSP00000380734.2	Q52LJ0-2
	FAM98B	ENST00000559431.1	TSL:5	c.259-286C>T		intron	N/A	ENSP00000453926.1	H0YNA1

Frequencies

GnomAD3 genomes

AF:

0.00000670

AC:

AN:

149358

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000193

AC:

AN:

155630

AF XY:

0.0000241

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:

0.0000497

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000286

AC:

AN:

1398782

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

690114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31508

American (AMR)

AF:

0.00

AC:

AN:

36274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25212

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35666

South Asian (SAS)

AF:

0.00

AC:

AN:

79314

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5492

European-Non Finnish (NFE)

AF:

0.0000334

AC:

AN:

1079128

Other (OTH)

AF:

0.0000518

AC:

AN:

57944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

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:

0.00000670

AC:

AN:

149358

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72704

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40228

American (AMR)

AF:

0.00

AC:

AN:

15004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4568

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67510

Other (OTH)

AF:

0.00

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

Pathogenic

0.81

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.97

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.37

MetaSVM

Uncertain

0.047

PhyloP100

2.3

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.60

Sift

Uncertain

0.018

Sift4G

Uncertain

0.015

Vest4

0.44

MutPred

0.54

Loss of catalytic residue at P317 (P = 1e-04)

MVP

0.75

MPC

0.52

ClinPred

0.85

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

gMVP

0.40

Mutation Taster

=67/33

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over