Genetic Variant FAM89B:p.Ala69Val (chr11-65572875-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001098785.2(FAM89B):c.206C>T(p.Ala69Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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. A69S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM89B
NM_001098785.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.317

Publications

0 publications found

Variant links:

Genes affected

FAM89B (HGNC:16708): (family with sequence similarity 89 member B) Predicted to enable transcription corepressor binding activity. Predicted to be involved in establishment of cell polarity; negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway; and positive regulation of cell migration. Predicted to be active in cytoplasm and lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

FAM89B links:

ZNRD2 (HGNC:11328): (zinc ribbon domain containing 2) This antigen is recognized by a subset of anti-centromere antibodies from patients with scleroderma and/or Sjogren's syndrome. Subcellular localization has not yet been established. [provided by RefSeq, Jul 2008]

ZNRD2 links:

ZNRD2-DT (HGNC:27384): (ZNRD2 divergent transcript)

ZNRD2-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05390662).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098785.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM89B	NM_001098785.2	MANE Select	c.206C>T	p.Ala69Val	missense	Exon 1 of 2	NP_001092255.1	Q8N5H3-3
FAM89B	NM_152832.3		c.206C>T	p.Ala69Val	missense	Exon 1 of 2	NP_690045.1	Q8N5H3-1
FAM89B	NM_001098784.2		c.206C>T	p.Ala69Val	missense	Exon 1 of 2	NP_001092254.1	Q8N5H3-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM89B	ENST00000530349.2	TSL:2 MANE Select	c.206C>T	p.Ala69Val	missense	Exon 1 of 2	ENSP00000431459.1	Q8N5H3-3
FAM89B	ENST00000316409.2	TSL:1	c.206C>T	p.Ala69Val	missense	Exon 1 of 2	ENSP00000314829.2	Q8N5H3-1
FAM89B	ENST00000449319.2	TSL:1	c.206C>T	p.Ala69Val	missense	Exon 1 of 2	ENSP00000402439.2	Q8N5H3-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1050914

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

500680

African (AFR)

AF:

0.00

AC:

AN:

21306

American (AMR)

AF:

0.00

AC:

AN:

7090

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12118

East Asian (EAS)

AF:

0.00

AC:

AN:

22958

South Asian (SAS)

AF:

0.00

AC:

AN:

19912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

904628

Other (OTH)

AF:

0.00

AC:

AN:

40684

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.45

M_CAP

Benign

0.036

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.1

PhyloP100

0.32

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.0

REVEL

Benign

0.026

Sift

Benign

0.30

Sift4G

Benign

0.31

Polyphen

0.71

Vest4

0.071

MutPred

0.13

Gain of MoRF binding (P = 0.1682)

MVP

0.088

MPC

0.71

ClinPred

0.073

GERP RS

1.9

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.030

gMVP

0.21

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over