8-12427711-C-G

Variant names:

• chr8-12427711-C-G
• rs201696967
• NM_001137610.3:c.838G>C

Variant summary

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

The NM_001137610.3(FAM86B2):​c.838G>C​(p.Val280Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V280M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000010 (0 hom., cov: 13)
  • Exomes 𝑓: 0.0000020 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761
• 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=0.13403317).

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.838G>C	p.Val280Leu	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
	FAM86B2	NR_148876.2		n.527G>C		non_coding_transcript_exon	Exon 5 of 6
	FAM86B2	NR_148877.2		n.446G>C		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.838G>C	p.Val280Leu	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
	FAM86B2	ENST00000942450.1		c.808G>C	p.Val270Leu	missense	Exon 7 of 8	ENSP00000612509.1
	FAM86B2	ENST00000870195.1		c.736G>C	p.Val246Leu	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes AF: 0.0000105 AC: 1 AN: 95346 Hom.: 0 Cov.: 13

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: 0.000342

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000200 AC: 2 AN: 1000112 Hom.: 1 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 498992

African (AFR) AF: 0.00 AC: 0 AN: 25860

American (AMR) AF: 0.00 AC: 0 AN: 31714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15956

East Asian (EAS) AF: 0.00 AC: 0 AN: 30390

South Asian (SAS) AF: 0.0000309 AC: 2 AN: 64648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3052

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 755462

Other (OTH) AF: 0.00 AC: 0 AN: 41964

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000105 AC: 1 AN: 95346 Hom.: 0 Cov.: 13 AF XY: 0.0000218 AC XY: 1 AN XY: 45922

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

African (AFR) AF: 0.00 AC: 0 AN: 27322

American (AMR) AF: 0.00 AC: 0 AN: 8818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1998

East Asian (EAS) AF: 0.00 AC: 0 AN: 3584

South Asian (SAS) AF: 0.000342 AC: 1 AN: 2928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 196

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 42824

Other (OTH) AF: 0.00 AC: 0 AN: 1202

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.3
DANN	Benign	0.91
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.049	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L
PhyloP100		-0.76
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.026
Sift	Benign	0.046	D
Sift4G	Benign	0.30	T
Polyphen		0.023	B
Vest4		0.31
MutPred		0.60		Gain of sheet (P = 0.0221)
MVP		0.093
MPC		1.7
ClinPred		0.085	T
GERP RS		-0.54
Varity_R		0.12
gMVP		0.54
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: rs201696967; hg19: chr8-12285220;