11-65573604-A-C

Position:

chr11-65573604-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001098785.2(FAM89B):c.533A>C(p.Asp178Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,611,260 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

FAM89B
NM_001098785.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.54

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:

Genome browser will be placed here

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=0.2547883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM89B	NM_001098785.2 linkuse as main transcript	c.533A>C	p.Asp178Ala	missense_variant	2/2	ENST00000530349.2	NP_001092255.1	Q8N5H3-3
FAM89B	NM_152832.3 linkuse as main transcript	c.494A>C	p.Asp165Ala	missense_variant	2/2		NP_690045.1	Q8N5H3-1
FAM89B	NM_001098784.2 linkuse as main transcript	c.*78A>C		3_prime_UTR_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.533A>C	p.Asp178Ala	missense_variant	2/2	2	NM_001098785.2	ENSP00000431459.1	Q8N5H3-3
FAM89B	ENST00000316409.2 linkuse as main transcript	c.494A>C	p.Asp165Ala	missense_variant	2/2	1		ENSP00000314829.2	Q8N5H3-1
FAM89B	ENST00000449319.2 linkuse as main transcript	c.*78A>C		3_prime_UTR_variant	2/2	1		ENSP00000402439.2	Q8N5H3-4
ZNRD2	ENST00000526433.1 linkuse as main transcript	c.*78A>C		3_prime_UTR_variant	3/3	3		ENSP00000435982.1	H0YEK1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

248438

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1459148

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000852

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000330

AC:

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

Oct 05, 2021

The c.533A>C (p.D178A) alteration is located in exon 2 (coding exon 2) of the FAM89B gene. This alteration results from a A to C substitution at nucleotide position 533, causing the aspartic acid (D) at amino acid position 178 to be replaced by an alanine (A). 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

0.94

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.84

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.026

D;D

Vest4

0.55

MVP

0.099

MPC

2.0

ClinPred

0.29

GERP RS

4.7

Varity_R

0.15

gMVP

0.92

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