Variant chr2-96894008-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001122646.3(FAM178B):c.1694C>G(p.Ser565Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,612,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict 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: 0.000021 ( 0 hom. )

Consequence

FAM178B
NM_001122646.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

Variant links:

Genes affected

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

FAM178B links:

FAM178B (HGNC:):

FAM178B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19487852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM178B	NM_001122646.3 linkuse as main transcript	c.1694C>G	p.Ser565Cys	missense_variant	14/17	ENST00000490605.3	NP_001116118.2	Q8IXR5-3B3KV66
FAM178B	NM_001172667.2 linkuse as main transcript	c.71C>G	p.Ser24Cys	missense_variant	2/5		NP_001166138.1	Q8IXR5-4
FAM178B	NM_016490.5 linkuse as main transcript	c.14C>G	p.Ser5Cys	missense_variant	2/5		NP_057574.2	Q8IXR5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM178B	ENST00000490605.3 linkuse as main transcript	c.1694C>G	p.Ser565Cys	missense_variant	14/17	5	NM_001122646.3	ENSP00000429896.1	Q8IXR5-3
FAM178B	ENST00000393526.6 linkuse as main transcript	c.14C>G	p.Ser5Cys	missense_variant	2/5	1		ENSP00000377160.2	Q8IXR5-2
FAM178B	ENST00000470789.5 linkuse as main transcript	n.126C>G		non_coding_transcript_exon_variant	2/5	1
FAM178B	ENST00000494172.1 linkuse as main transcript	n.146C>G		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000722

AC:

AN:

249304

Hom.:

AF XY:

0.0000666

AC XY:

AN XY:

135132

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000522

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1460438

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000672

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

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.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000330

AC:

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

May 09, 2023

The c.1694C>G (p.S565C) 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 1694, causing the serine (S) at amino acid position 565 to be replaced by a cysteine (C). 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

0.095

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.88

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.086

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.0030

D;D

Vest4

0.30

MVP

0.62

MPC

0.10

ClinPred

0.35

GERP RS

3.7

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.9

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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