8-12428716-C-T

Variant names:

• chr8-12428716-C-T
• rs1253093343
• NM_001137610.3:c.659G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001137610.3(FAM86B2):​c.659G>A​(p.Arg220Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. R220M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000075 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0000095 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0120
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0845916).

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.659G>A	p.Arg220Lys	missense	Exon 6 of 8	NP_001131082.1	P0C5J1
	FAM86B2	NR_148876.2		n.431+265G>A		intron	N/A
	FAM86B2	NR_148877.2		n.350+265G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM86B2	ENST00000262365.9	TSL:5 MANE Select	c.659G>A	p.Arg220Lys	missense	Exon 6 of 8	ENSP00000262365.4	P0C5J1
	FAM86B2	ENST00000942450.1		c.629G>A	p.Arg210Lys	missense	Exon 6 of 8	ENSP00000612509.1
	FAM86B2	ENST00000870195.1		c.557G>A	p.Arg186Lys	missense	Exon 5 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes AF: 0.00000752 AC: 1 AN: 132984 Hom.: 0 Cov.: 21

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: 0.0000161

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000344 AC: 4 AN: 116272 AF XY: 0.0000485

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000501

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000612

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000950 AC: 12 AN: 1263050 Hom.: 0 Cov.: 29 AF XY: 0.0000112 AC XY: 7 AN XY: 627494

African (AFR) AF: 0.00 AC: 0 AN: 27434

American (AMR) AF: 0.0000280 AC: 1 AN: 35744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22660

East Asian (EAS) AF: 0.00 AC: 0 AN: 35528

South Asian (SAS) AF: 0.0000137 AC: 1 AN: 73092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3716

European-Non Finnish (NFE) AF: 0.0000103 AC: 10 AN: 973450

Other (OTH) AF: 0.00 AC: 0 AN: 53278

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000752 AC: 1 AN: 132984 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 64104

African (AFR) AF: 0.00 AC: 0 AN: 34910

American (AMR) AF: 0.00 AC: 0 AN: 12728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3126

East Asian (EAS) AF: 0.00 AC: 0 AN: 4178

South Asian (SAS) AF: 0.00 AC: 0 AN: 3732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000161 AC: 1 AN: 62130

Other (OTH) AF: 0.00 AC: 0 AN: 1758

Alfa AF: 0.00 Hom.: 0

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	0.093
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.90
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.35	N
PhyloP100		0.012
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.075
Sift	Benign	0.75	T
Sift4G	Benign	0.94	T
Polyphen		0.0020	B
Vest4		0.057
MutPred		0.59		Gain of ubiquitination at R220 (P = 0.0128)
MVP		0.068
MPC		2.4
ClinPred		0.027	T
GERP RS		-2.3
Varity_R		0.055
gMVP		0.35
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1253093343; hg19: chr8-12286225;