1-20553857-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207334.3(FAM43B):​c.884G>A​(p.Arg295Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000473 in 1,269,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

FAM43B
NM_207334.3 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.650
Variant links:
Genes affected
FAM43B (HGNC:31791): (family with sequence similarity 43 member B)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.056969494).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM43BNM_207334.3 linkc.884G>A p.Arg295Gln missense_variant Exon 1 of 1 ENST00000332947.6 NP_997217.1 Q6ZT52

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM43BENST00000332947.6 linkc.884G>A p.Arg295Gln missense_variant Exon 1 of 1 6 NM_207334.3 ENSP00000331397.4 Q6ZT52

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000253
AC:
2
AN:
79208
Hom.:
0
AF XY:
0.0000221
AC XY:
1
AN XY:
45286
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000409
Gnomad SAS exome
AF:
0.0000615
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000473
AC:
6
AN:
1269390
Hom.:
0
Cov.:
31
AF XY:
0.00000479
AC XY:
3
AN XY:
625724
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000391
Gnomad4 SAS exome
AF:
0.0000299
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000198
Gnomad4 OTH exome
AF:
0.0000198
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.884G>A (p.R295Q) alteration is located in exon 1 (coding exon 1) of the FAM43B gene. This alteration results from a G to A substitution at nucleotide position 884, causing the arginine (R) at amino acid position 295 to be replaced by a glutamine (Q). 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
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0073
T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.59
T
M_CAP
Uncertain
0.28
D
MetaRNN
Benign
0.057
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.030
N
REVEL
Benign
0.024
Sift
Benign
0.18
T
Sift4G
Benign
0.80
T
Polyphen
0.35
B
Vest4
0.046
MutPred
0.15
Loss of MoRF binding (P = 0.0285);
MVP
0.18
ClinPred
0.030
T
GERP RS
1.7
Varity_R
0.045
gMVP
0.15

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: rs886234326; hg19: chr1-20880350; API