Genetic Variant FAM86B2:p.Glu296Lys (chr8-12427663-C-T) – 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.886G>A(p.Glu296Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 2 hom., cov: 15)

Exomes 𝑓: 0.000070 ( 24 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B2
NM_001137610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.512

Publications

1 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=0.16454592).

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.886G>A	p.Glu296Lys	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2		n.575G>A		non_coding_transcript_exon	Exon 5 of 6
FAM86B2	NR_148877.2		n.494G>A		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.886G>A	p.Glu296Lys	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
FAM86B2	ENST00000942450.1		c.856G>A	p.Glu286Lys	missense	Exon 7 of 8	ENSP00000612509.1
FAM86B2	ENST00000870195.1		c.784G>A	p.Glu262Lys	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes

AF:

0.0000404

AC:

AN:

99086

Hom.:

Cov.:

show subpopulations

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:

0.0000910

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000712

AC:

AN:

168570

AF XY:

0.0000755

show subpopulations

Gnomad AFR exome

AF:

0.000275

Gnomad AMR exome

AF:

0.0000824

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000138

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000674

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000699

AC:

AN:

1001970

Hom.:

Cov.:

AF XY:

0.0000680

AC XY:

AN XY:

499824

show subpopulations

African (AFR)

AF:

0.0000775

AC:

AN:

25800

American (AMR)

AF:

0.0000633

AC:

AN:

31614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15944

East Asian (EAS)

AF:

0.000197

AC:

AN:

30394

South Asian (SAS)

AF:

0.0000155

AC:

AN:

64602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3098

European-Non Finnish (NFE)

AF:

0.0000753

AC:

AN:

756628

Other (OTH)

AF:

0.0000476

AC:

AN:

41982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.402

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000404

AC:

AN:

99086

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

47860

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28928

American (AMR)

AF:

0.00

AC:

AN:

9180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2046

East Asian (EAS)

AF:

0.00

AC:

AN:

3658

South Asian (SAS)

AF:

0.00

AC:

AN:

3068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.0000910

AC:

AN:

43964

Other (OTH)

AF:

0.00

AC:

AN:

1258

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000888

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.78

M_CAP

Benign

0.0033

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

PhyloP100

0.51

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.2

REVEL

Benign

0.071

Sift

Benign

0.072

Sift4G

Benign

0.18

Polyphen

0.033

Vest4

0.44

MVP

0.043

MPC

1.9

ClinPred

0.025

GERP RS

1.8

Varity_R

0.054

gMVP

0.61

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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