rs1249208835

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-65572881-C-A
• chr11-65572881-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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]

ACMG classification

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=0.10745713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM89B	NM_001098785.2	c.212C>A	p.Ala71Asp	missense_variant	Exon 1 of 2	ENST00000530349.2	NP_001092255.1
FAM89B	NM_152832.3	c.212C>A	p.Ala71Asp	missense_variant	Exon 1 of 2		NP_690045.1
FAM89B	NM_001098784.2	c.212C>A	p.Ala71Asp	missense_variant	Exon 1 of 2		NP_001092254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM89B	ENST00000530349.2	c.212C>A	p.Ala71Asp	missense_variant	Exon 1 of 2	2	NM_001098785.2	ENSP00000431459.1

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

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: 0.00000110

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.93	N;N;N
REVEL	Benign	0.074
Sift	Benign	0.58	T;D;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.014	.;.;B
Vest4		0.26
MutPred		0.27		Loss of MoRF binding (P = 0.1263);Loss of MoRF binding (P = 0.1263);Loss of MoRF binding (P = 0.1263);
MVP		0.15
MPC		1.2
ClinPred		0.18	T
GERP RS		3.8
Varity_R		0.13
gMVP		0.24

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.

Other links and lift over

hg19: chr11-65340352;