NM_001098785.2:c.391T>C

Variant names:

• chr11-65573462-T-C
• NM_001098785.2:c.391T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.70
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19749588).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM89B	NM_001098785.2	MANE Select	c.391T>C	p.Cys131Arg	missense	Exon 2 of 2	NP_001092255.1	Q8N5H3-3
	FAM89B	NM_152832.3		c.352T>C	p.Cys118Arg	missense	Exon 2 of 2	NP_690045.1	Q8N5H3-1
	FAM89B	NM_001098784.2		c.401T>C	p.Leu134Pro	missense	Exon 2 of 2	NP_001092254.1	Q8N5H3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM89B	ENST00000530349.2	TSL:2 MANE Select	c.391T>C	p.Cys131Arg	missense	Exon 2 of 2	ENSP00000431459.1	Q8N5H3-3
	FAM89B	ENST00000316409.2	TSL:1	c.352T>C	p.Cys118Arg	missense	Exon 2 of 2	ENSP00000314829.2	Q8N5H3-1
	FAM89B	ENST00000449319.2	TSL:1	c.401T>C	p.Leu134Pro	missense	Exon 2 of 2	ENSP00000402439.2	Q8N5H3-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461732 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727164

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111908

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.066
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.97	T
PhyloP100		3.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.012	D
Vest4		0.41
MVP		0.17
MPC		2.3
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.81
gMVP		0.47
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

hg19: chr11-65340933;