chr3-194687583-A-C

Variant summary

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

The NM_153690.5(FAM43A):​c.757A>C​(p.Ile253Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

FAM43A
NM_153690.5 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.80
Variant links:
Genes affected
FAM43A (HGNC:26888): (family with sequence similarity 43 member A)

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=0.23217216).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM43ANM_153690.5 linkc.757A>C p.Ile253Leu missense_variant Exon 1 of 1 ENST00000329759.6 NP_710157.2 Q8N2R8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM43AENST00000329759.6 linkc.757A>C p.Ile253Leu missense_variant Exon 1 of 1 6 NM_153690.5 ENSP00000371397.1 Q8N2R8

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.757A>C (p.I253L) alteration is located in exon 1 (coding exon 1) of the FAM43A gene. This alteration results from a A to C substitution at nucleotide position 757, causing the isoleucine (I) at amino acid position 253 to be replaced by a leucine (L). 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
Pathogenic
0.87
BayesDel_addAF
Uncertain
0.085
D
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.25
T
Eigen
Benign
-0.072
Eigen_PC
Benign
0.052
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.42
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.8
N
REVEL
Uncertain
0.35
Sift
Uncertain
0.0040
D
Sift4G
Benign
0.30
T
Polyphen
0.0090
B
Vest4
0.42
MutPred
0.41
Loss of catalytic residue at L258 (P = 0.0265);
MVP
0.51
ClinPred
0.92
D
GERP RS
2.7
Varity_R
0.37
gMVP
0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-194408312; API