11-65572772-G-T

Variant names:

• chr11-65572772-G-T
• NM_001098785.2:c.103G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001098785.2(FAM89B):​c.103G>T​(p.Gly35Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM89B NM_001098785.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM89B	NM_001098785.2	c.103G>T	p.Gly35Trp	missense_variant	Exon 1 of 2	ENST00000530349.2	NP_001092255.1
FAM89B	NM_152832.3	c.103G>T	p.Gly35Trp	missense_variant	Exon 1 of 2		NP_690045.1
FAM89B	NM_001098784.2	c.103G>T	p.Gly35Trp	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.103G>T	p.Gly35Trp	missense_variant	Exon 1 of 2	2	NM_001098785.2	ENSP00000431459.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1049146 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 502310

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 24, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.103G>T (p.G35W) alteration is located in exon 1 (coding exon 1) of the FAM89B gene. This alteration results from a G to T substitution at nucleotide position 103, causing the glycine (G) at amino acid position 35 to be replaced by a tryptophan (W). 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	0.97
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;.;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Pathogenic	0.77	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-0.52	T
PrimateAI	Pathogenic	0.96	D
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.48
MutPred		0.64		Loss of glycosylation at S34 (P = 0.0273);Loss of glycosylation at S34 (P = 0.0273);Loss of glycosylation at S34 (P = 0.0273);
MVP		0.21
MPC		1.9
ClinPred		1.0	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.44
gMVP		0.49

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: chr11-65340243;