chr8-12427729-G-A

Variant names:

• chr8-12427729-G-A
• rs768854601
• NM_001137610.3:c.820C>T

Variant summary

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

The NM_001137610.3(FAM86B2):​c.820C>T​(p.Arg274Trp) 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 0.00011 (0 hom., cov: 13)
  • Exomes 𝑓: 0.000078 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17
• Publications: 1 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=0.04779005).

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.820C>T	p.Arg274Trp	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
	FAM86B2	NR_148876.2		n.509C>T		non_coding_transcript_exon	Exon 5 of 6
	FAM86B2	NR_148877.2		n.428C>T		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.820C>T	p.Arg274Trp	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
	FAM86B2	ENST00000942450.1		c.790C>T	p.Arg264Trp	missense	Exon 7 of 8	ENSP00000612509.1
	FAM86B2	ENST00000870195.1		c.718C>T	p.Arg240Trp	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes AF: 0.000109 AC: 10 AN: 91634 Hom.: 0 Cov.: 13

Gnomad AFR AF: 0.0000380

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000356

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000362

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000967

Gnomad OTH AF: 0.000880

GnomAD2 exomes AF: 0.000122 AC: 20 AN: 164008 AF XY: 0.000132

Gnomad AFR exome AF: 0.0000950

Gnomad AMR exome AF: 0.000620

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000701

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000492

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000781 AC: 78 AN: 998656 Hom.: 9 Cov.: 32 AF XY: 0.0000843 AC XY: 42 AN XY: 498442

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

African (AFR) AF: 0.0000387 AC: 1 AN: 25860

American (AMR) AF: 0.000597 AC: 19 AN: 31822

Ashkenazi Jewish (ASJ) AF: 0.0000625 AC: 1 AN: 15990

East Asian (EAS) AF: 0.000197 AC: 6 AN: 30384

South Asian (SAS) AF: 0.000123 AC: 8 AN: 64830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2946

European-Non Finnish (NFE) AF: 0.0000503 AC: 38 AN: 754840

Other (OTH) AF: 0.000119 AC: 5 AN: 41948

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000000366374), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000109 AC: 10 AN: 91710 Hom.: 0 Cov.: 13 AF XY: 0.000136 AC XY: 6 AN XY: 44058

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

African (AFR) AF: 0.0000379 AC: 1 AN: 26396

American (AMR) AF: 0.000356 AC: 3 AN: 8436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1928

East Asian (EAS) AF: 0.00 AC: 0 AN: 3438

South Asian (SAS) AF: 0.000364 AC: 1 AN: 2750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 178

European-Non Finnish (NFE) AF: 0.0000967 AC: 4 AN: 41344

Other (OTH) AF: 0.000864 AC: 1 AN: 1158

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000813723), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 Hom.: 0

ExAC AF: 0.000129 AC: 11

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	0.087
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.043
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.013	D
Polyphen		0.018	B
Vest4		0.19
MVP		0.043
MPC		1.8
ClinPred		0.071	T
GERP RS		0.60
Varity_R		0.14
gMVP		0.44
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: rs768854601; hg19: chr8-12285238;