Variant 2-96877947-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001122646.3(FAM178B):c.1950C>A(p.Asp650Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FAM178B
NM_001122646.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.448

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM178B	NM_001122646.3 linkuse as main transcript	c.1950C>A	p.Asp650Glu	missense_variant	16/17	ENST00000490605.3	NP_001116118.2	Q8IXR5-3B3KV66
FAM178B	NM_001172667.2 linkuse as main transcript	c.327C>A	p.Asp109Glu	missense_variant	4/5		NP_001166138.1	Q8IXR5-4
FAM178B	NM_016490.5 linkuse as main transcript	c.270C>A	p.Asp90Glu	missense_variant	4/5		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.1950C>A	p.Asp650Glu	missense_variant	16/17	5	NM_001122646.3	ENSP00000429896.1	Q8IXR5-3
FAM178B	ENST00000393526.6 linkuse as main transcript	c.270C>A	p.Asp90Glu	missense_variant	4/5	1		ENSP00000377160.2	Q8IXR5-2
FAM178B	ENST00000470789.5 linkuse as main transcript	n.382C>A		non_coding_transcript_exon_variant	4/5	1
FAM178B	ENST00000494172.1 linkuse as main transcript	n.402C>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152266

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250048

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

0.00000205

AC:

AN:

1461530

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

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:

0.00000656

AC:

AN:

152384

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74518

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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 30, 2024

The c.1950C>A (p.D650E) 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 1950, causing the aspartic acid (D) at amino acid position 650 to be replaced by a glutamic acid (E). 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

Pathogenic

0.69

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.53

D;D

MetaSVM

Benign

-0.55

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.8

D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0030

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.62

MVP

0.48

MPC

0.38

ClinPred

0.91

GERP RS

2.4

gMVP

0.24

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