NM_001122646.3:c.488C>T

Variant summary

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

The NM_001122646.3(FAM178B):​c.488C>T​(p.Pro163Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000576 in 1,562,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P163R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

FAM178B
NM_001122646.3 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.322
Variant links:
Genes affected
FAM178B (HGNC:28036): (family with sequence similarity 178 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=0.06582266).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM178BNM_001122646.3 linkc.488C>T p.Pro163Leu missense_variant Exon 3 of 17 ENST00000490605.3 NP_001116118.2 Q8IXR5-3B3KV66

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM178BENST00000490605.3 linkc.488C>T p.Pro163Leu missense_variant Exon 3 of 17 5 NM_001122646.3 ENSP00000429896.1 Q8IXR5-3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152176
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000117
AC:
2
AN:
171648
Hom.:
0
AF XY:
0.0000109
AC XY:
1
AN XY:
91772
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000793
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000142
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000496
AC:
7
AN:
1410376
Hom.:
0
Cov.:
30
AF XY:
0.00000574
AC XY:
4
AN XY:
696580
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000269
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000553
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152176
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000284
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
1.2
DANN
Benign
0.38
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.066
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.24
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.013
Sift
Benign
0.24
T
Sift4G
Benign
0.33
T
Vest4
0.040
MVP
0.13
MPC
0.069
ClinPred
0.10
T
GERP RS
0.10
gMVP
0.056

Splicing

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: rs559244924; hg19: chr2-97637714; API