Genetic Variant FAM89B:p.Gly3Arg (chr11-65572676-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001098785.2(FAM89B):c.7G>A(p.Gly3Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000919 in 1,164,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

FAM89B
NM_001098785.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3131457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM89B	NM_001098785.2 link	c.7G>A	p.Gly3Arg	missense_variant	Exon 1 of 2	ENST00000530349.2	NP_001092255.1	Q8N5H3-3
FAM89B	NM_152832.3 link	c.7G>A	p.Gly3Arg	missense_variant	Exon 1 of 2		NP_690045.1	Q8N5H3-1
FAM89B	NM_001098784.2 link	c.7G>A	p.Gly3Arg	missense_variant	Exon 1 of 2		NP_001092254.1	Q8N5H3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM89B	ENST00000530349.2 link	c.7G>A	p.Gly3Arg	missense_variant	Exon 1 of 2	2	NM_001098785.2	ENSP00000431459.1		Q8N5H3-3

Frequencies

GnomAD3 genomes

AF:

0.0000668

AC:

AN:

149676

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000134

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000956

AC:

AN:

1014624

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

480152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000366

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000561

Gnomad4 NFE exome

AF:

0.000100

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.0000668

AC:

AN:

149676

Hom.:

Cov.:

AF XY:

0.0000685

AC XY:

AN XY:

73006

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000134

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000642

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7G>A (p.G3R) alteration is located in exon 1 (coding exon 1) of the FAM89B gene. This alteration results from a G to A substitution at nucleotide position 7, causing the glycine (G) at amino acid position 3 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

Pathogenic

0.88

BayesDel_addAF

Benign

0.0033

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

.;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.66

T;T;T

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.63

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-2.2

N;D;N

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.35

MutPred

0.38

Gain of phosphorylation at S6 (P = 0.1261);Gain of phosphorylation at S6 (P = 0.1261);Gain of phosphorylation at S6 (P = 0.1261);

MVP

0.12

MPC

1.9

ClinPred

0.97

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.13

gMVP

0.45

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