rs766238665

Variant names:

• chr8-12427742-G-C
• rs766238665
• NM_001137610.3:c.807C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-12427742-G-C
• chr8-12427742-G-A

Variant summary

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

The NM_001137610.3(FAM86B2):​c.807C>G​(p.Cys269Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000011 (0 hom., cov: 12)
  • Exomes 𝑓: 0.0000071 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.779
• 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=0.2932465).

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.807C>G	p.Cys269Trp	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
	FAM86B2	NR_148876.2		n.496C>G		non_coding_transcript_exon	Exon 5 of 6
	FAM86B2	NR_148877.2		n.415C>G		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.807C>G	p.Cys269Trp	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
	FAM86B2	ENST00000942450.1		c.777C>G	p.Cys259Trp	missense	Exon 7 of 8	ENSP00000612509.1
	FAM86B2	ENST00000870195.1		c.705C>G	p.Cys235Trp	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes AF: 0.0000115 AC: 1 AN: 87140 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000127

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: 0.00000681 AC: 1 AN: 146814 AF XY: 0.0000123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000156

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000710 AC: 7 AN: 986518 Hom.: 2 Cov.: 27 AF XY: 0.00000203 AC XY: 1 AN XY: 493000

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25522

American (AMR) AF: 0.0000316 AC: 1 AN: 31666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15920

East Asian (EAS) AF: 0.00 AC: 0 AN: 30254

South Asian (SAS) AF: 0.00 AC: 0 AN: 64546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2892

European-Non Finnish (NFE) AF: 0.00000402 AC: 3 AN: 745508

Other (OTH) AF: 0.0000723 AC: 3 AN: 41514

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0338994), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000115 AC: 1 AN: 87140 Hom.: 0 Cov.: 12 AF XY: 0.0000240 AC XY: 1 AN XY: 41600

African (AFR) AF: 0.00 AC: 0 AN: 25210

American (AMR) AF: 0.000127 AC: 1 AN: 7884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1850

East Asian (EAS) AF: 0.00 AC: 0 AN: 3252

South Asian (SAS) AF: 0.00 AC: 0 AN: 2610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 176

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 39466

Other (OTH) AF: 0.00 AC: 0 AN: 1070

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000122 AC: 1

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	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.78
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Benign	0.081
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.37		Gain of MoRF binding (P = 0.0177)
MVP		0.15
MPC		4.0
ClinPred		0.85	D
GERP RS		0.86
Varity_R		0.58
gMVP		0.66
Mutation Taster		=84/16	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: rs766238665; hg19: chr8-12285251;