8-12427666-T-C

Variant names:

• chr8-12427666-T-C
• rs1408792631
• NM_001137610.3:c.883A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001137610.3(FAM86B2):​c.883A>G​(p.Thr295Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 𝑓 0.000020 (0 hom., cov: 15)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06854272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3	c.883A>G	p.Thr295Ala	missense_variant	Exon 7 of 8	ENST00000262365.9	NP_001131082.1
FAM86B2	NR_148876.2	n.572A>G		non_coding_transcript_exon_variant	Exon 5 of 6
FAM86B2	NR_148877.2	n.491A>G		non_coding_transcript_exon_variant	Exon 4 of 5
FAM86B2	NR_148878.2	n.772A>G		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.883A>G	p.Thr295Ala	missense_variant	Exon 7 of 8	5	NM_001137610.3	ENSP00000262365.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2 AN: 98806 Hom.: 0 Cov.: 15 FAILED QC

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000456

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000202 AC: 2 AN: 98806 Hom.: 0 Cov.: 15 AF XY: 0.0000210 AC XY: 1 AN XY: 47728

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000456

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.0
DANN	Benign	0.65
DEOGEN2	Benign	0.0049	T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.55	T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.069	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.35	N;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.3	N;D;N
REVEL	Benign	0.028
Sift	Benign	0.38	T;D;T
Sift4G	Benign	0.63	T;T;T
Polyphen		0.0020	B;.;.
Vest4		0.099
MutPred		0.51		Gain of helix (P = 0.2059);.;.;
MVP		0.043
MPC		1.8
ClinPred		0.035	T
GERP RS		-2.3
Varity_R		0.029
gMVP		0.27

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: rs1408792631; hg19: chr8-12285175;