Genetic Variant FAM193B:p.Arg752His (chr5-177524226-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001190946.3(FAM193B):c.2255G>A(p.Arg752His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,546,404 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 0.000033 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

FAM193B
NM_001190946.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.46

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22040913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM193B	NM_001190946.3 link	c.2255G>A	p.Arg752His	missense_variant	Exon 6 of 9	ENST00000514747.6	NP_001177875.1	Q6IPW0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM193B	ENST00000514747.6 link	c.2255G>A	p.Arg752His	missense_variant	Exon 6 of 9	5	NM_001190946.3	ENSP00000422131.1		Q96PV7-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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

GnomAD3 exomes

AF:

0.0000342

AC:

AN:

175312

Hom.:

AF XY:

0.0000422

AC XY:

AN XY:

94784

show subpopulations

Gnomad AFR exome

AF:

0.000343

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1394088

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

687146

show subpopulations

Gnomad4 AFR exome

AF:

0.000159

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000131

Gnomad4 FIN exome

AF:

0.0000617

Gnomad4 NFE exome

AF:

0.00000927

Gnomad4 OTH exome

AF:

0.0000523

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000337

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000244

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000333

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2255G>A (p.R752H) alteration is located in exon 6 (coding exon 6) of the FAM193B gene. This alteration results from a G to A substitution at nucleotide position 2255, causing the arginine (R) at amino acid position 752 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.032

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.70

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.13

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.051

Vest4

0.57

MVP

0.20

MPC

0.78

ClinPred

0.39

GERP RS

5.6

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over