NM_001137610.3:c.614G>T

Variant names:

• chr8-12428761-C-A
• rs758719069
• NM_001137610.3:c.614G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001137610.3(FAM86B2):​c.614G>T​(p.Gly205Val) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 9.6e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.68

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 Uncertain_significance. Variant got 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3	c.614G>T	p.Gly205Val	missense_variant	Exon 6 of 8	ENST00000262365.9	NP_001131082.1
FAM86B2	NR_148876.2	n.431+220G>T		intron_variant	Intron 4 of 5
FAM86B2	NR_148877.2	n.350+220G>T		intron_variant	Intron 3 of 4
FAM86B2	NR_148878.2	n.631+220G>T		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B2	ENST00000262365.9	c.614G>T	p.Gly205Val	missense_variant	Exon 6 of 8	5	NM_001137610.3	ENSP00000262365.4

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD3 exomes AF: 0.00000700 AC: 1 AN: 142898 Hom.: 0 AF XY: 0.0000130 AC XY: 1 AN XY: 76858

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000476

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

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: 9.58e-7 AC: 1 AN: 1044030 Hom.: 0 Cov.: 30 AF XY: 0.00000190 AC XY: 1 AN XY: 525430

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000293

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 18

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T;.
Eigen	Benign	-0.071
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0080	T
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.2	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.018	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.96	D;.
Vest4		0.66
MutPred		0.76		Loss of catalytic residue at G205 (P = 0.1204);.;
MVP		0.36
MPC		3.4
ClinPred		0.98	D
GERP RS		0.22
Varity_R		0.56
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs758719069; hg19: chr8-12286270;