8-12428724-G-T

Variant names:

• chr8-12428724-G-T
• rs1210344444
• NM_001137610.3:c.651C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001137610.3(FAM86B2):​c.651C>A​(p.Asp217Glu) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000051 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000053 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.250
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022926211).
• BP6: Variant 8-12428724-G-T is Benign according to our data. Variant chr8-12428724-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2459774.Status of the report is criteria_provided_single_submitter, 1 stars.

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.651C>A	p.Asp217Glu	missense	Exon 6 of 8	NP_001131082.1	P0C5J1
	FAM86B2	NR_148876.2		n.431+257C>A		intron	N/A
	FAM86B2	NR_148877.2		n.350+257C>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.651C>A	p.Asp217Glu	missense	Exon 6 of 8	ENSP00000262365.4	P0C5J1
	FAM86B2	ENST00000942450.1		c.621C>A	p.Asp207Glu	missense	Exon 6 of 8	ENSP00000612509.1
	FAM86B2	ENST00000870195.1		c.549C>A	p.Asp183Glu	missense	Exon 5 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes AF: 0.0000513 AC: 6 AN: 116874 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00146

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: 0.000117 AC: 14 AN: 119302 AF XY: 0.000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000534 AC: 61 AN: 1142542 Hom.: 0 Cov.: 28 AF XY: 0.0000509 AC XY: 29 AN XY: 569446

⚠️ 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: 24988

American (AMR) AF: 0.00 AC: 0 AN: 33368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17974

East Asian (EAS) AF: 0.00122 AC: 43 AN: 35314

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 71018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3212

European-Non Finnish (NFE) AF: 0.00000229 AC: 2 AN: 871970

Other (OTH) AF: 0.000313 AC: 15 AN: 47954

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000513 AC: 6 AN: 116956 Hom.: 0 Cov.: 19 AF XY: 0.0000530 AC XY: 3 AN XY: 56638

⚠️ 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: 30638

American (AMR) AF: 0.00 AC: 0 AN: 11266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2316

East Asian (EAS) AF: 0.00147 AC: 6 AN: 4086

South Asian (SAS) AF: 0.00 AC: 0 AN: 3562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 54180

Other (OTH) AF: 0.00 AC: 0 AN: 1504

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000860221), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.63
DANN	Benign	0.94
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0073	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.00085	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.17	N
PhyloP100		-0.25
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.011
Sift	Benign	0.51	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.061
MutPred		0.39		Gain of disorder (P = 0.1738)
MVP		0.043
MPC		1.9
ClinPred		0.014	T
GERP RS		0.17
Varity_R		0.033
gMVP		0.21
Mutation Taster		=100/0	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: rs1210344444; hg19: chr8-12286233;