chr8-12428747-C-A

Variant names:

• chr8-12428747-C-A
• rs1371781729
• NM_001137610.3:c.628G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001137610.3(FAM86B2):​c.628G>T​(p.Ala210Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 19)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10797775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3	c.628G>T	p.Ala210Ser	missense_variant	Exon 6 of 8	ENST00000262365.9	NP_001131082.1
FAM86B2	NR_148876.2	n.431+234G>T		intron_variant	Intron 4 of 5
FAM86B2	NR_148877.2	n.350+234G>T		intron_variant	Intron 3 of 4
FAM86B2	NR_148878.2	n.631+234G>T		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B2	ENST00000262365.9	c.628G>T	p.Ala210Ser	missense_variant	Exon 6 of 8	5	NM_001137610.3	ENSP00000262365.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 121754 Hom.: 0 Cov.: 19 FAILED QC

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: 0.00

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: 8.97e-7 AC: 1 AN: 1114490 Hom.: 0 Cov.: 30 AF XY: 0.00000179 AC XY: 1 AN XY: 559214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 121754 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 58134

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.0
DANN	Benign	0.87
DEOGEN2	Benign	0.0015	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.39	N;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.28	N;N
REVEL	Benign	0.039
Sift	Benign	0.37	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.0020	B;.
Vest4		0.039
MutPred		0.66		Gain of disorder (P = 0.0188);.;
MVP		0.043
MPC		3.0
ClinPred		0.052	T
GERP RS		0.17
Varity_R		0.034
gMVP		0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs1371781729; hg19: chr8-12286256;