NM_001098785.2:c.130G>T

Variant names:

• chr11-65572799-G-T
• rs955284004
• NM_001098785.2:c.130G>T

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.130G>T​(p.Val44Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,206,544 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: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: FAM89B NM_001098785.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74
• 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=0.12077972).

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.130G>T	p.Val44Phe	missense	Exon 1 of 2	NP_001092255.1	Q8N5H3-3
	FAM89B	NM_152832.3		c.130G>T	p.Val44Phe	missense	Exon 1 of 2	NP_690045.1	Q8N5H3-1
	FAM89B	NM_001098784.2		c.130G>T	p.Val44Phe	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.130G>T	p.Val44Phe	missense	Exon 1 of 2	ENSP00000431459.1	Q8N5H3-3
	FAM89B	ENST00000316409.2	TSL:1	c.130G>T	p.Val44Phe	missense	Exon 1 of 2	ENSP00000314829.2	Q8N5H3-1
	FAM89B	ENST00000449319.2	TSL:1	c.130G>T	p.Val44Phe	missense	Exon 1 of 2	ENSP00000402439.2	Q8N5H3-4

Frequencies

GnomAD3 genomes AF: 0.00000669 AC: 1 AN: 149426 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000315 AC: 1 AN: 31698 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000164

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000189 AC: 2 AN: 1057010 Hom.: 0 Cov.: 31 AF XY: 0.00000197 AC XY: 1 AN XY: 507584

African (AFR) AF: 0.00 AC: 0 AN: 21428

American (AMR) AF: 0.000154 AC: 2 AN: 13014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13636

East Asian (EAS) AF: 0.00 AC: 0 AN: 19778

South Asian (SAS) AF: 0.00 AC: 0 AN: 29350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2784

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 897296

Other (OTH) AF: 0.00 AC: 0 AN: 40232

GnomAD4 genome AF: 0.00000669 AC: 1 AN: 149534 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72938

African (AFR) AF: 0.00 AC: 0 AN: 41308

American (AMR) AF: 0.0000664 AC: 1 AN: 15054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3420

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66790

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

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	0.63
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.7
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.086
Sift	Benign	0.041	D
Sift4G	Benign	0.061	T
Polyphen		0.31	B
Vest4		0.49
MutPred		0.16		Loss of phosphorylation at Y45 (P = 0.1187)
MVP		0.12
MPC		1.4
ClinPred		0.16	T
GERP RS		0.76
PromoterAI		-0.027	Neutral
Varity_R		0.094
gMVP		0.50
Mutation Taster		=74/26	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: rs955284004; hg19: chr11-65340270;