chr8-12427702-T-G

Variant names:

• chr8-12427702-T-G
• rs1585364789
• NM_001137610.3:c.847A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001137610.3(FAM86B2):​c.847A>C​(p.Thr283Pro) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T283A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 14)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95
• Publications: 0 publications found

Genes affected

FAM86B2 (HGNC:32222): (family with sequence similarity 86 member B2) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

FAM66A (HGNC:30444): (family with sequence similarity 66 member A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.792

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137610.3. 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
	FAM86B2	NM_001137610.3	MANE Select	c.847A>C	p.Thr283Pro	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
	FAM86B2	NR_148876.2		n.536A>C		non_coding_transcript_exon	Exon 5 of 6
	FAM86B2	NR_148877.2		n.455A>C		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM86B2	ENST00000262365.9	TSL:5 MANE Select	c.847A>C	p.Thr283Pro	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
	FAM86B2	ENST00000942450.1		c.817A>C	p.Thr273Pro	missense	Exon 7 of 8	ENSP00000612509.1
	FAM86B2	ENST00000870195.1		c.745A>C	p.Thr249Pro	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1001552 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 499682

African (AFR) AF: 0.00 AC: 0 AN: 25866

American (AMR) AF: 0.00 AC: 0 AN: 31640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15958

East Asian (EAS) AF: 0.00 AC: 0 AN: 30392

South Asian (SAS) AF: 0.00 AC: 0 AN: 64570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3080

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 756558

Other (OTH) AF: 0.00 AC: 0 AN: 41994

GnomAD4 genome Cov.: 14

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.049	T
Eigen	Benign	0.098
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		4.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.70		Loss of stability (P = 0.0658)
MVP		0.27
MPC		3.5
ClinPred		0.93	D
GERP RS		1.8
Varity_R		0.67
gMVP		0.85
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1585364789; hg19: chr8-12285211;