chr11-65572916-C-T

Variant names:

• chr11-65572916-C-T
• rs1857159080
• NM_001098785.2:c.247C>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.247C>T​(p.Pro83Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000458 in 1,070,264 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P83L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: FAM89B NM_001098785.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87
• 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=0.11551145).

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.247C>T	p.Pro83Ser	missense	Exon 1 of 2	NP_001092255.1	Q8N5H3-3
	FAM89B	NM_152832.3		c.247C>T	p.Pro83Ser	missense	Exon 1 of 2	NP_690045.1	Q8N5H3-1
	FAM89B	NM_001098784.2		c.247C>T	p.Pro83Ser	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.247C>T	p.Pro83Ser	missense	Exon 1 of 2	ENSP00000431459.1	Q8N5H3-3
	FAM89B	ENST00000316409.2	TSL:1	c.247C>T	p.Pro83Ser	missense	Exon 1 of 2	ENSP00000314829.2	Q8N5H3-1
	FAM89B	ENST00000449319.2	TSL:1	c.247C>T	p.Pro83Ser	missense	Exon 1 of 2	ENSP00000402439.2	Q8N5H3-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000458 AC: 49 AN: 1070264 Hom.: 0 Cov.: 31 AF XY: 0.0000452 AC XY: 23 AN XY: 508998

African (AFR) AF: 0.00 AC: 0 AN: 22180

American (AMR) AF: 0.00 AC: 0 AN: 7764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13360

East Asian (EAS) AF: 0.00 AC: 0 AN: 25216

South Asian (SAS) AF: 0.00 AC: 0 AN: 20084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2990

European-Non Finnish (NFE) AF: 0.0000513 AC: 47 AN: 916010

Other (OTH) AF: 0.0000473 AC: 2 AN: 42326

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.30
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.77	T
PhyloP100		3.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.087
Sift	Benign	0.10	T
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.27		Gain of phosphorylation at P83 (P = 0.0176)
MVP		0.076
MPC		1.1
ClinPred		0.47	T
GERP RS		2.4
PromoterAI		0.0081	Neutral
Varity_R		0.082
gMVP		0.30
Mutation Taster		=77/23	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: rs1857159080; hg19: chr11-65340387;