chr11-65572881-C-A

Variant names:

• chr11-65572881-C-A
• rs1249208835
• NM_001098785.2:c.212C>A

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.212C>A​(p.Ala71Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000948 in 1,054,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A71V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: FAM89B NM_001098785.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• 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=0.10745713).

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.212C>A	p.Ala71Asp	missense	Exon 1 of 2	NP_001092255.1	Q8N5H3-3
	FAM89B	NM_152832.3		c.212C>A	p.Ala71Asp	missense	Exon 1 of 2	NP_690045.1	Q8N5H3-1
	FAM89B	NM_001098784.2		c.212C>A	p.Ala71Asp	missense	Exon 1 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.212C>A	p.Ala71Asp	missense	Exon 1 of 2	ENSP00000431459.1	Q8N5H3-3
	FAM89B	ENST00000316409.2	TSL:1	c.212C>A	p.Ala71Asp	missense	Exon 1 of 2	ENSP00000314829.2	Q8N5H3-1
	FAM89B	ENST00000449319.2	TSL:1	c.212C>A	p.Ala71Asp	missense	Exon 1 of 2	ENSP00000402439.2	Q8N5H3-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.48e-7 AC: 1 AN: 1054784 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 502406

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21458

American (AMR) AF: 0.00 AC: 0 AN: 7180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12364

East Asian (EAS) AF: 0.00 AC: 0 AN: 23386

South Asian (SAS) AF: 0.00 AC: 0 AN: 19874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2792

European-Non Finnish (NFE) AF: 0.00000110 AC: 1 AN: 907084

Other (OTH) AF: 0.00 AC: 0 AN: 40982

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.87
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.074
Sift	Benign	0.58	T
Sift4G	Benign	0.51	T
Polyphen		0.014	B
Vest4		0.26
MutPred		0.27		Loss of MoRF binding (P = 0.1263)
MVP		0.15
MPC		1.2
ClinPred		0.18	T
GERP RS		3.8
PromoterAI		0.017	Neutral
Varity_R		0.13
gMVP		0.24
Mutation Taster		=85/15	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: rs1249208835; hg19: chr11-65340352;