chr9-131261331-C-T

Variant summary

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

The NM_033387.4(FAM78A):​c.343G>A​(p.Asp115Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000942 in 1,591,546 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 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

FAM78A
NM_033387.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84
Variant links:
Genes affected
FAM78A (HGNC:25465): (family with sequence similarity 78 member A)

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=0.3837794).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM78ANM_033387.4 linkc.343G>A p.Asp115Asn missense_variant Exon 2 of 2 ENST00000372271.4 NP_203745.2 Q5JUQ0Q8N2W3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM78AENST00000372271.4 linkc.343G>A p.Asp115Asn missense_variant Exon 2 of 2 1 NM_033387.4 ENSP00000361345.3 Q5JUQ0

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152012
Hom.:
0
Cov.:
31
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000176
AC:
4
AN:
227058
Hom.:
0
AF XY:
0.0000242
AC XY:
3
AN XY:
123742
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.0000305
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:
0.00000950
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000973
AC:
14
AN:
1439534
Hom.:
0
Cov.:
34
AF XY:
0.0000112
AC XY:
8
AN XY:
716004
show subpopulations
Gnomad4 AFR exome
AF:
0.0000603
Gnomad4 AMR exome
AF:
0.0000692
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:
0.00000723
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152012
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74232
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.343G>A (p.D115N) alteration is located in exon 2 (coding exon 2) of the FAM78A gene. This alteration results from a G to A substitution at nucleotide position 343, causing the aspartic acid (D) at amino acid position 115 to be replaced by an asparagine (N). 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
Uncertain
0.35
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.46
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.096
.;T;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.38
T;T;T
MetaSVM
Benign
-0.55
T
MutationAssessor
Benign
1.9
.;L;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.26
Sift
Benign
0.094
T;T;T
Sift4G
Benign
0.072
T;T;T
Polyphen
1.0
D;D;.
Vest4
0.53
MVP
0.34
MPC
1.7
ClinPred
0.47
T
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.17
gMVP
0.66

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: rs369808057; hg19: chr9-134136718; API