11-65573630-A-G

Variant names:

• chr11-65573630-A-G
• rs765216859
• NM_001098785.2:c.559A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001098785.2(FAM89B):​c.559A>G​(p.Ile187Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,606,186 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: FAM89B NM_001098785.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.092623055).

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.559A>G	p.Ile187Val	missense	Exon 2 of 2	NP_001092255.1	Q8N5H3-3
	FAM89B	NM_152832.3		c.520A>G	p.Ile174Val	missense	Exon 2 of 2	NP_690045.1	Q8N5H3-1
	FAM89B	NM_001098784.2		c.*104A>G		3_prime_UTR	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.559A>G	p.Ile187Val	missense	Exon 2 of 2	ENSP00000431459.1	Q8N5H3-3
	FAM89B	ENST00000316409.2	TSL:1	c.520A>G	p.Ile174Val	missense	Exon 2 of 2	ENSP00000314829.2	Q8N5H3-1
	FAM89B	ENST00000449319.2	TSL:1	c.*104A>G		3_prime_UTR	Exon 2 of 2	ENSP00000402439.2	Q8N5H3-4

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

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: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000861 AC: 21 AN: 243884 AF XY: 0.0000980

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000171

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000261 AC: 380 AN: 1454062 Hom.: 0 Cov.: 32 AF XY: 0.000241 AC XY: 174 AN XY: 723396

African (AFR) AF: 0.0000299 AC: 1 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86132

European-Finnish (FIN) AF: 0.0000209 AC: 1 AN: 47780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5434

European-Non Finnish (NFE) AF: 0.000322 AC: 358 AN: 1110686

Other (OTH) AF: 0.000332 AC: 20 AN: 60262

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74304

African (AFR) AF: 0.0000724 AC: 3 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000210 Hom.: 0

Bravo AF: 0.000121

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000109

EpiControl AF: 0.000178

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	Benign	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.091
Eigen_PC	Benign	0.032
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.84	T
PhyloP100		1.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.087
Sift	Benign	0.19	T
Sift4G	Benign	0.087	T
Vest4		0.31
MVP		0.014
MPC		0.79
ClinPred		0.044	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.60
Mutation Taster		=90/10	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

dbSNP: rs765216859; hg19: chr11-65341101;