1-20553026-G-A

Variant summary

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

The NM_207334.3(FAM43B):​c.53G>A​(p.Cys18Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,300 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FAM43B
NM_207334.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82
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 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=0.11772388).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM43BNM_207334.3 linkc.53G>A p.Cys18Tyr 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.53G>A p.Cys18Tyr missense_variant Exon 1 of 1 6 NM_207334.3 ENSP00000331397.4 Q6ZT52

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461300
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727004
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
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
Dec 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.53G>A (p.C18Y) 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 53, causing the cysteine (C) at amino acid position 18 to be replaced by a tyrosine (Y). 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
0.12
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Uncertain
24
DANN
Benign
0.97
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.038
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
1.1
L
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.025
Sift
Benign
0.038
D
Sift4G
Uncertain
0.049
D
Polyphen
0.071
B
Vest4
0.097
MutPred
0.20
Gain of helix (P = 0.0128);
MVP
0.31
ClinPred
0.57
D
GERP RS
4.3
Varity_R
0.37
gMVP
0.52

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: rs1557530918; hg19: chr1-20879519; API