8-12427702-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3	c.847A>C	p.Thr283Pro	missense_variant	Exon 7 of 8	ENST00000262365.9	NP_001131082.1
FAM86B2	NR_148876.2	n.536A>C		non_coding_transcript_exon_variant	Exon 5 of 6
FAM86B2	NR_148877.2	n.455A>C		non_coding_transcript_exon_variant	Exon 4 of 5
FAM86B2	NR_148878.2	n.736A>C		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B2	ENST00000262365.9	c.847A>C	p.Thr283Pro	missense_variant	Exon 7 of 8	5	NM_001137610.3	ENSP00000262365.4

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

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.: 14

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Benign	0.098
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.84	T;T;D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	2.9	M;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0040	D;D;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1585364789; hg19: chr8-12285211;