1-166070399-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001017961.5(FAM78B):​c.628C>T​(p.Arg210Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,110 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

FAM78B
NM_001017961.5 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73
Variant links:
Genes affected
FAM78B (HGNC:13495): (family with sequence similarity 78 member B)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.4169607).
BS2
High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM78BNM_001017961.5 linkc.628C>T p.Arg210Trp missense_variant Exon 2 of 2 ENST00000354422.4 NP_001017961.1 Q5VT40F1T0K0
FAM78BNM_001320302.2 linkc.264-9736C>T intron_variant Intron 1 of 1 NP_001307231.1 F1T0K0
FAM78BNR_135199.2 linkn.1381C>T non_coding_transcript_exon_variant Exon 2 of 3
FAM78BNR_163271.1 linkn.1135C>T non_coding_transcript_exon_variant Exon 2 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM78BENST00000354422.4 linkc.628C>T p.Arg210Trp missense_variant Exon 2 of 2 2 NM_001017961.5 ENSP00000346404.3 Q5VT40

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251176
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135740
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000981
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461820
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152290
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
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
Alfa
AF:
0.000169
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.628C>T (p.R210W) alteration is located in exon 2 (coding exon 2) of the FAM78B gene. This alteration results from a C to T substitution at nucleotide position 628, causing the arginine (R) at amino acid position 210 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
Uncertain
0.40
BayesDel_addAF
Uncertain
0.023
T
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.24
T;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Benign
0.52
D
LIST_S2
Pathogenic
0.98
.;D
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.42
T;T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
1.9
L;L
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-5.2
D;D
REVEL
Benign
0.21
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
1.0
D;D
Vest4
0.53
MVP
0.23
MPC
1.6
ClinPred
0.71
D
GERP RS
5.7
Varity_R
0.57
gMVP
0.63

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: rs202158388; hg19: chr1-166039636; API