rs758719069

Variant names:

• chr8-12428761-C-T
• rs758719069
• NM_001137610.3:c.614G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-12428761-C-T
• chr8-12428761-C-A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001137610.3(FAM86B2):​c.614G>A​(p.Gly205Asp) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000062 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00013 (33 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41876847).

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.614G>A	p.Gly205Asp	missense	Exon 6 of 8	NP_001131082.1	P0C5J1
	FAM86B2	NR_148876.2		n.431+220G>A		intron	N/A
	FAM86B2	NR_148877.2		n.350+220G>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.614G>A	p.Gly205Asp	missense	Exon 6 of 8	ENSP00000262365.4	P0C5J1
	FAM86B2	ENST00000942450.1		c.584G>A	p.Gly195Asp	missense	Exon 6 of 8	ENSP00000612509.1
	FAM86B2	ENST00000870195.1		c.512G>A	p.Gly171Asp	missense	Exon 5 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes AF: 0.0000620 AC: 7 AN: 112898 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.0000345

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: 0.000110

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000630 AC: 9 AN: 142898 AF XY: 0.0000390

Gnomad AFR exome AF: 0.000122

Gnomad AMR exome AF: 0.0000476

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000105

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000134 AC: 140 AN: 1044030 Hom.: 33 Cov.: 30 AF XY: 0.000143 AC XY: 75 AN XY: 525430

African (AFR) AF: 0.00 AC: 0 AN: 22918

American (AMR) AF: 0.0000293 AC: 1 AN: 34140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20370

East Asian (EAS) AF: 0.00 AC: 0 AN: 34342

South Asian (SAS) AF: 0.000104 AC: 7 AN: 67014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3200

European-Non Finnish (NFE) AF: 0.000167 AC: 130 AN: 777394

Other (OTH) AF: 0.0000436 AC: 2 AN: 45908

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000620 AC: 7 AN: 112898 Hom.: 0 Cov.: 18 AF XY: 0.0000187 AC XY: 1 AN XY: 53528

African (AFR) AF: 0.0000345 AC: 1 AN: 28956

American (AMR) AF: 0.00 AC: 0 AN: 10272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2708

East Asian (EAS) AF: 0.00 AC: 0 AN: 3690

South Asian (SAS) AF: 0.00 AC: 0 AN: 3070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.000110 AC: 6 AN: 54528

Other (OTH) AF: 0.00 AC: 0 AN: 1442

Alfa AF: 0.0000613 Hom.: 0

ExAC AF: 0.0000579 AC: 4

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	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.68
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.13
Sift	Benign	0.056	T
Sift4G	Uncertain	0.024	D
Polyphen		0.097	B
Vest4		0.32
MutPred		0.76		Loss of catalytic residue at G205 (P = 0.0397)
MVP		0.13
MPC		2.2
ClinPred		0.10	T
GERP RS		0.22
Varity_R		0.40
gMVP		0.59
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs758719069; hg19: chr8-12286270;