Variant 2-96893960-T-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.1742A>G(p.Gln581Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

FAM178B
NM_001122646.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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=0.18357599).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM178B	NM_001122646.3 linkuse as main transcript	c.1742A>G	p.Gln581Arg	missense_variant	14/17	ENST00000490605.3	NP_001116118.2	Q8IXR5-3B3KV66
FAM178B	NM_001172667.2 linkuse as main transcript	c.119A>G	p.Gln40Arg	missense_variant	2/5		NP_001166138.1	Q8IXR5-4
FAM178B	NM_016490.5 linkuse as main transcript	c.62A>G	p.Gln21Arg	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.1742A>G	p.Gln581Arg	missense_variant	14/17	5	NM_001122646.3	ENSP00000429896.1	Q8IXR5-3
FAM178B	ENST00000393526.6 linkuse as main transcript	c.62A>G	p.Gln21Arg	missense_variant	2/5	1		ENSP00000377160.2	Q8IXR5-2
FAM178B	ENST00000470789.5 linkuse as main transcript	n.174A>G		non_coding_transcript_exon_variant	2/5	1
FAM178B	ENST00000494172.1 linkuse as main transcript	n.194A>G		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249832

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460762

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726710

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:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Aug 14, 2024

The c.1742A>G (p.Q581R) alteration is located in exon 14 (coding exon 14) of the FAM178B gene. This alteration results from a A to G substitution at nucleotide position 1742, causing the glutamine (Q) at amino acid position 581 to be replaced by an arginine (R). 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

0.086

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.015

Eigen_PC

Benign

-0.024

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.044

Sift

Benign

0.069

T;T

Sift4G

Benign

0.083

T;D

Vest4

0.21

MVP

0.44

MPC

0.19

ClinPred

0.31

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

gMVP

0.12

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.

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