dbSNP rs370017170: FAM193B:p.Pro517Thr (chr5-177524932-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001190946.3(FAM193B):c.1549C>A(p.Pro517Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000398 in 1,506,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

FAM193B
NM_001190946.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97

Publications

0 publications found

Variant links:

Genes affected

FAM193B (HGNC:25524): (family with sequence similarity 193 member B) Located in cytoplasm; nuclear speck; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

FAM193B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.103847444).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190946.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM193B	NM_001190946.3	MANE Select	c.1549C>A	p.Pro517Thr	missense	Exon 6 of 9	NP_001177875.1	Q96PV7-3
FAM193B	NM_001410826.1		c.1789C>A	p.Pro597Thr	missense	Exon 7 of 10	NP_001397755.1	Q96PV7-1
FAM193B	NM_001366500.1		c.1450C>A	p.Pro484Thr	missense	Exon 7 of 10	NP_001353429.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM193B	ENST00000514747.6	TSL:5 MANE Select	c.1549C>A	p.Pro517Thr	missense	Exon 6 of 9	ENSP00000422131.1	Q96PV7-3
FAM193B	ENST00000505569.5	TSL:1	n.556C>A		non_coding_transcript_exon	Exon 1 of 4
FAM193B	ENST00000506955.5	TSL:1	n.*2779C>A		non_coding_transcript_exon	Exon 9 of 12	ENSP00000424961.1	D6REQ2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000592

AC:

AN:

168844

AF XY:

0.0000112

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000540

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:

0.00

GnomAD4 exome

AF:

0.00000369

AC:

AN:

1354606

Hom.:

Cov.:

AF XY:

0.00000453

AC XY:

AN XY:

662708

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29908

American (AMR)

AF:

0.00

AC:

AN:

26894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19740

East Asian (EAS)

AF:

0.00

AC:

AN:

37702

South Asian (SAS)

AF:

0.00

AC:

AN:

68446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5272

European-Non Finnish (NFE)

AF:

0.00000377

AC:

AN:

1061492

Other (OTH)

AF:

0.0000180

AC:

AN:

55548

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

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:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

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:

0.00000378

ExAC

AF:

0.00000844

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

Benign

0.066

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.88

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

M_CAP

Benign

0.017

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

PhyloP100

3.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.52

REVEL

Benign

0.023

Sift

Benign

0.25

Sift4G

Uncertain

0.058

Vest4

0.20

MVP

0.082

MPC

0.40

ClinPred

0.15

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.13

Mutation Taster

=77/23

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