19-16185721-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014077.4(FAM32A):​c.172C>T​(p.Arg58Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000257 in 1,557,276 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

FAM32A
NM_014077.4 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85
Variant links:
Genes affected
FAM32A (HGNC:24563): (family with sequence similarity 32 member A) Enables RNA binding activity. Predicted to be involved in apoptotic process. Located in nucleolus and nucleoplasm. [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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33740965).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM32ANM_014077.4 linkc.172C>T p.Arg58Trp missense_variant Exon 2 of 4 ENST00000263384.12 NP_054796.1 Q9Y421-1A0A024R7I4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM32AENST00000263384.12 linkc.172C>T p.Arg58Trp missense_variant Exon 2 of 4 1 NM_014077.4 ENSP00000263384.6 Q9Y421-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.12e-7
AC:
1
AN:
1405088
Hom.:
0
Cov.:
31
AF XY:
0.00000144
AC XY:
1
AN XY:
693462
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:
9.25e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000921
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.172C>T (p.R58W) alteration is located in exon 2 (coding exon 2) of the FAM32A gene. This alteration results from a C to T substitution at nucleotide position 172, causing the arginine (R) at amino acid position 58 to be replaced by a tryptophan (W). 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
0.89
BayesDel_addAF
Benign
-0.026
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
.;T;.;T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.19
N
LIST_S2
Uncertain
0.86
D;D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.34
T;T;T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Uncertain
2.1
.;M;.;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-4.6
.;D;.;.
REVEL
Benign
0.16
Sift
Benign
0.039
.;D;.;.
Sift4G
Uncertain
0.047
D;T;T;D
Polyphen
0.022
.;B;.;.
Vest4
0.74
MutPred
0.29
.;Loss of catalytic residue at R58 (P = 0.0965);Loss of catalytic residue at R58 (P = 0.0965);.;
MVP
0.092
MPC
1.1
ClinPred
0.99
D
GERP RS
2.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.36
gMVP
0.71

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: rs777564641; hg19: chr19-16296532; API