chr5-177524410-C-T

Variant summary

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

The NM_001190946.3(FAM193B):​c.2071G>A​(p.Glu691Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000348 in 1,438,810 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: not found (cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

FAM193B
NM_001190946.3 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00
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]

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=0.2052778).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM193BNM_001190946.3 linkc.2071G>A p.Glu691Lys 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
FAM193BENST00000514747.6 linkc.2071G>A p.Glu691Lys missense_variant Exon 6 of 9 5 NM_001190946.3 ENSP00000422131.1 Q96PV7-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000469
AC:
1
AN:
213148
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
116544
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000190
GnomAD4 exome
AF:
0.00000348
AC:
5
AN:
1438810
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
714210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000182
Gnomad4 OTH exome
AF:
0.0000505
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 17, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2071G>A (p.E691K) 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 2071, causing the glutamic acid (E) at amino acid position 691 to be replaced by a lysine (K). 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
Benign
-0.075
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
23
DANN
Uncertain
1.0
Eigen
Benign
0.069
Eigen_PC
Benign
0.10
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-0.78
T
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.74
N
REVEL
Benign
0.073
Sift
Benign
0.040
D
Sift4G
Benign
0.64
T
Vest4
0.45
MVP
0.13
MPC
0.45
ClinPred
0.38
T
GERP RS
5.4
gMVP
0.19

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

LitVar

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

Other links and lift over

dbSNP: rs1396847941; hg19: chr5-176951411; API