NM_001137610.3:c.838G>T

Variant names:

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

Variant summary

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

The NM_001137610.3(FAM86B2):​c.838G>T​(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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 13)
  • Exomes 𝑓: 0.0000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B2 NM_001137610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761

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=0.13634041).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3	c.838G>T	p.Val280Leu	missense_variant	Exon 7 of 8	ENST00000262365.9	NP_001131082.1
FAM86B2	NR_148876.2	n.527G>T		non_coding_transcript_exon_variant	Exon 5 of 6
FAM86B2	NR_148877.2	n.446G>T		non_coding_transcript_exon_variant	Exon 4 of 5
FAM86B2	NR_148878.2	n.727G>T		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B2	ENST00000262365.9	c.838G>T	p.Val280Leu	missense_variant	Exon 7 of 8	5	NM_001137610.3	ENSP00000262365.4

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000100 AC: 1 AN: 1000108 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 498988

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000329

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.: 13

ExAC AF: 0.0000115 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.6
DANN	Benign	0.91
DEOGEN2	Benign	0.0095	T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.045	N
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N;.;N
REVEL	Benign	0.026
Sift	Benign	0.046	D;.;T
Sift4G	Benign	0.30	T;D;T
Polyphen		0.023	B;.;.
Vest4		0.31
MutPred		0.60		Gain of sheet (P = 0.0221);.;.;
MVP		0.082
MPC		1.7
ClinPred		0.044	T
GERP RS		-0.54
Varity_R		0.12
gMVP		0.54

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: rs201696967; hg19: chr8-12285220;