Genetic Variant NM_001137610.3:c.838G>T (chr8-12427711-C-A) – ACMG Classification: Likely_benign (-2 pts)

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>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. 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: not found (cov: 13)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B2
NM_001137610.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.761

Publications

0 publications found

Variant links:

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]

FAM86B2 links:

FAM66A (HGNC:30444): (family with sequence similarity 66 member A)

FAM66A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13634041).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM86B2	NM_001137610.3	MANE Select	c.838G>T	p.Val280Leu	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2		n.527G>T		non_coding_transcript_exon	Exon 5 of 6
FAM86B2	NR_148877.2		n.446G>T		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM86B2	ENST00000262365.9	TSL:5 MANE Select	c.838G>T	p.Val280Leu	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
FAM86B2	ENST00000942450.1		c.808G>T	p.Val270Leu	missense	Exon 7 of 8	ENSP00000612509.1
FAM86B2	ENST00000870195.1		c.736G>T	p.Val246Leu	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

166928

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000100

AC:

AN:

1000108

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

498988

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25860

American (AMR)

AF:

0.00

AC:

AN:

31714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15956

East Asian (EAS)

AF:

0.0000329

AC:

AN:

30390

South Asian (SAS)

AF:

0.00

AC:

AN:

64648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3052

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

755460

Other (OTH)

AF:

0.00

AC:

AN:

41964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000115

AC:

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

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.6

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0095

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.045

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0072

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

PhyloP100

-0.76

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.7

REVEL

Benign

0.026

Sift

Benign

0.046

Sift4G

Benign

0.30

Polyphen

0.023

Vest4

0.31

MutPred

0.60

Gain of sheet (P = 0.0221)

MVP

0.082

MPC

1.7

ClinPred

0.044

GERP RS

-0.54

Varity_R

0.12

gMVP

0.54

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over