Variant 2-96877946-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001122646.3(FAM178B):c.1951C>A(p.Leu651Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,613,914 control chromosomes in the GnomAD database, including 2 homozygotes. 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 (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 2 hom. )

Consequence

FAM178B
NM_001122646.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13193017).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FAM178B	NM_001122646.3 linkuse as main transcript	c.1951C>A	p.Leu651Met	missense_variant	16/17	ENST00000490605.3	NP_001116118.2
FAM178B	NM_001172667.2 linkuse as main transcript	c.328C>A	p.Leu110Met	missense_variant	4/5		NP_001166138.1
FAM178B	NM_016490.5 linkuse as main transcript	c.271C>A	p.Leu91Met	missense_variant	4/5		NP_057574.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM178B	ENST00000490605.3 linkuse as main transcript	c.1951C>A	p.Leu651Met	missense_variant	16/17	5	NM_001122646.3	ENSP00000429896	P1	Q8IXR5-3
FAM178B	ENST00000393526.6 linkuse as main transcript	c.271C>A	p.Leu91Met	missense_variant	4/5	1		ENSP00000377160		Q8IXR5-2
FAM178B	ENST00000470789.5 linkuse as main transcript	n.383C>A		non_coding_transcript_exon_variant	4/5	1
FAM178B	ENST00000494172.1 linkuse as main transcript	n.403C>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152270

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:

0.000192

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

250002

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

135494

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:

0.000849

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1461526

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

727064

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:

0.000719

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152388

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 04, 2022

The c.1951C>A (p.L651M) alteration is located in exon 16 (coding exon 16) of the FAM178B gene. This alteration results from a C to A substitution at nucleotide position 1951, causing the leucine (L) at amino acid position 651 to be replaced by a methionine (M). 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

0.16

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.69

T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.46

MutationTaster

Benign

0.95

N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.29

Sift

Uncertain

0.0050

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.49

MVP

0.51

MPC

0.39

ClinPred

0.40

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

gMVP

0.33

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