8-12427726-C-T

Variant names:

• chr8-12427726-C-T
• rs1467328058
• NM_001137610.3:c.823G>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001137610.3(FAM86B2):​c.823G>A​(p.Ala275Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 13)
  • Exomes 𝑓: 0.0000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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 Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30037084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3	c.823G>A	p.Ala275Thr	missense_variant	Exon 7 of 8	ENST00000262365.9	NP_001131082.1
FAM86B2	NR_148876.2	n.512G>A		non_coding_transcript_exon_variant	Exon 5 of 6
FAM86B2	NR_148877.2	n.431G>A		non_coding_transcript_exon_variant	Exon 4 of 5
FAM86B2	NR_148878.2	n.712G>A		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.823G>A	p.Ala275Thr	missense_variant	Exon 7 of 8	5	NM_001137610.3	ENSP00000262365.4

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000100 AC: 1 AN: 1000002 Hom.: 0 Cov.: 33 AF XY: 0.00000200 AC XY: 1 AN XY: 498970

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: 0.00000132

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.6
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0051	T;T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.6	N;.;N
REVEL	Benign	0.037
Sift	Benign	0.090	T;.;T
Sift4G	Benign	0.12	T;D;T
Polyphen		0.20	B;.;.
Vest4		0.16
MutPred		0.36		Gain of phosphorylation at A275 (P = 0.0915);.;.;
MVP		0.082
MPC		1.7
ClinPred		0.14	T
GERP RS		0.60
Varity_R		0.034
gMVP		0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs1467328058; hg19: chr8-12285235;