Variant 11-65573462-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_001098785.2(FAM89B):c.391T>C(p.Cys131Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,732 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: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FAM89B
NM_001098785.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19749588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM89B	NM_001098785.2 linkuse as main transcript	c.391T>C	p.Cys131Arg	missense_variant	2/2	ENST00000530349.2	NP_001092255.1	Q8N5H3-3
FAM89B	NM_152832.3 linkuse as main transcript	c.352T>C	p.Cys118Arg	missense_variant	2/2		NP_690045.1	Q8N5H3-1
FAM89B	NM_001098784.2 linkuse as main transcript	c.401T>C	p.Leu134Pro	missense_variant	2/2		NP_001092254.1	Q8N5H3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM89B	ENST00000530349.2 linkuse as main transcript	c.391T>C	p.Cys131Arg	missense_variant	2/2	2	NM_001098785.2	ENSP00000431459.1	Q8N5H3-3
FAM89B	ENST00000316409.2 linkuse as main transcript	c.352T>C	p.Cys118Arg	missense_variant	2/2	1		ENSP00000314829.2	Q8N5H3-1
FAM89B	ENST00000449319.2 linkuse as main transcript	c.401T>C	p.Leu134Pro	missense_variant	2/2	1		ENSP00000402439.2	Q8N5H3-4
ZNRD2	ENST00000526433.1 linkuse as main transcript	c.257T>C	p.Leu86Pro	missense_variant	3/3	3		ENSP00000435982.1	H0YEK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727164

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

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

May 04, 2023

The c.391T>C (p.C131R) alteration is located in exon 2 (coding exon 2) of the FAM89B gene. This alteration results from a T to C substitution at nucleotide position 391, causing the cysteine (C) at amino acid position 131 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

0.69

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

.;T

Eigen

Benign

0.066

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.40

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.012

D;D

Vest4

0.41

MVP

0.17

MPC

2.3

ClinPred

0.99

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.81

gMVP

0.47

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over