rs750400187

Variant names:

• chr8-12427740-C-T
• rs750400187
• NM_001137610.3:c.809G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001137610.3(FAM86B2):​c.809G>A​(p.Arg270Gln) 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000090 (0 hom., cov: 12)
  • Exomes 𝑓: 0.000026 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.21
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03414327).

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.809G>A	p.Arg270Gln	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
	FAM86B2	NR_148876.2		n.498G>A		non_coding_transcript_exon	Exon 5 of 6
	FAM86B2	NR_148877.2		n.417G>A		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.809G>A	p.Arg270Gln	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
	FAM86B2	ENST00000942450.1		c.779G>A	p.Arg260Gln	missense	Exon 7 of 8	ENSP00000612509.1
	FAM86B2	ENST00000870195.1		c.707G>A	p.Arg236Gln	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes AF: 0.0000452 AC: 4 AN: 88502 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.000157

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000403 AC: 6 AN: 148804 AF XY: 0.0000363

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000220

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000268

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000263 AC: 26 AN: 989178 Hom.: 5 Cov.: 28 AF XY: 0.0000223 AC XY: 11 AN XY: 494152

African (AFR) AF: 0.000470 AC: 12 AN: 25532

American (AMR) AF: 0.000158 AC: 5 AN: 31678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15932

East Asian (EAS) AF: 0.0000330 AC: 1 AN: 30272

South Asian (SAS) AF: 0.0000155 AC: 1 AN: 64566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2896

European-Non Finnish (NFE) AF: 0.00000535 AC: 4 AN: 747742

Other (OTH) AF: 0.0000721 AC: 3 AN: 41582

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000903 AC: 8 AN: 88574 Hom.: 0 Cov.: 12 AF XY: 0.0000707 AC XY: 3 AN XY: 42424

African (AFR) AF: 0.000196 AC: 5 AN: 25516

American (AMR) AF: 0.00 AC: 0 AN: 8054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1860

East Asian (EAS) AF: 0.00 AC: 0 AN: 3326

South Asian (SAS) AF: 0.00 AC: 0 AN: 2648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 168

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 40122

Other (OTH) AF: 0.00270 AC: 3 AN: 1110

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000970 AC: 8

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	0.074
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0050
DANN	Benign	0.93
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.74	N
PhyloP100		-5.2
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.031
Sift	Benign	0.65	T
Sift4G	Benign	0.60	T
Polyphen		0.014	B
Vest4		0.078
MVP		0.068
MPC		2.0
ClinPred		0.045	T
GERP RS		-3.6
Varity_R		0.023
gMVP		0.22
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs750400187; hg19: chr8-12285249;