Variant 2-96894036-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001122646.3(FAM178B):c.1666C>G(p.Arg556Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000869 in 1,610,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R556W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

FAM178B
NM_001122646.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

FAM178B (HGNC:28036): (family with sequence similarity 178 member B)

FAM178B links:

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=0.3053118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM178B	NM_001122646.3 linkuse as main transcript	c.1666C>G	p.Arg556Gly	missense_variant	14/17	ENST00000490605.3
FAM178B	NM_001172667.2 linkuse as main transcript	c.43C>G	p.Arg15Gly	missense_variant	2/5
FAM178B	NM_016490.5 linkuse as main transcript	c.-15C>G		5_prime_UTR_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM178B	ENST00000490605.3 linkuse as main transcript	c.1666C>G	p.Arg556Gly	missense_variant	14/17	5	NM_001122646.3	P1	Q8IXR5-3
FAM178B	ENST00000393526.6 linkuse as main transcript	c.-15C>G		5_prime_UTR_variant	2/5	1			Q8IXR5-2
FAM178B	ENST00000470789.5 linkuse as main transcript	n.98C>G		non_coding_transcript_exon_variant	2/5	1
FAM178B	ENST00000494172.1 linkuse as main transcript	n.118C>G		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

AF:

0.00000892

AC:

AN:

1458216

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725184

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:

0.00000990

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.00

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

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.1666C>G (p.R556G) alteration is located in exon 14 (coding exon 14) of the FAM178B gene. This alteration results from a C to G substitution at nucleotide position 1666, causing the arginine (R) at amino acid position 556 to be replaced by a glycine (G). 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

Benign

0.10

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

0.053

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.71

M_CAP

Benign

0.037

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.045

Sift

Uncertain

0.024

Sift4G

Uncertain

0.037

Vest4

0.33

MVP

0.48

MPC

0.16

ClinPred

0.85

GERP RS

4.6

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over