chr11-65572902-C-T

Variant names:

• chr11-65572902-C-T
• rs905404078
• NM_001098785.2:c.233C>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.233C>T​(p.Ala78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,328 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 0.0000066 (0 hom., 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: 2.21
• 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=0.078305125).

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.233C>T	p.Ala78Val	missense	Exon 1 of 2	NP_001092255.1	Q8N5H3-3
	FAM89B	NM_152832.3		c.233C>T	p.Ala78Val	missense	Exon 1 of 2	NP_690045.1	Q8N5H3-1
	FAM89B	NM_001098784.2		c.233C>T	p.Ala78Val	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.233C>T	p.Ala78Val	missense	Exon 1 of 2	ENSP00000431459.1	Q8N5H3-3
	FAM89B	ENST00000316409.2	TSL:1	c.233C>T	p.Ala78Val	missense	Exon 1 of 2	ENSP00000314829.2	Q8N5H3-1
	FAM89B	ENST00000449319.2	TSL:1	c.233C>T	p.Ala78Val	missense	Exon 1 of 2	ENSP00000402439.2	Q8N5H3-4

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1063888 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 506352

African (AFR) AF: 0.00 AC: 0 AN: 21864

American (AMR) AF: 0.00 AC: 0 AN: 7506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13006

East Asian (EAS) AF: 0.00 AC: 0 AN: 24632

South Asian (SAS) AF: 0.00 AC: 0 AN: 19820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2856

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 912386

Other (OTH) AF: 0.00 AC: 0 AN: 41792

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151328 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73954

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10176

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67752

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Asia WGS AF: 0.000289 AC: 1 AN: 3476

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	0.090
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.91	T
PhyloP100		2.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.072
Sift	Benign	0.15	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.068
MutPred		0.099		Loss of glycosylation at P80 (P = 0.0987)
MVP		0.14
MPC		0.74
ClinPred		0.079	T
GERP RS		1.9
PromoterAI		0.019	Neutral
Varity_R		0.029
gMVP		0.17
Mutation Taster		=84/16	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: rs905404078; hg19: chr11-65340373;