dbSNP rs1585364789: FAM86B2:p.Thr283Ala (chr8-12427702-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001137610.3(FAM86B2):c.847A>G(p.Thr283Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000016 in 1,001,550 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T283T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 14)

Exomes 𝑓: 0.000016 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B2
NM_001137610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.95

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 -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

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.847A>G	p.Thr283Ala	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2		n.536A>G		non_coding_transcript_exon	Exon 5 of 6
FAM86B2	NR_148877.2		n.455A>G		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.847A>G	p.Thr283Ala	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
FAM86B2	ENST00000942450.1		c.817A>G	p.Thr273Ala	missense	Exon 7 of 8	ENSP00000612509.1
FAM86B2	ENST00000870195.1		c.745A>G	p.Thr249Ala	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

96058

Hom.:

Cov.:

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

AF:

0.0000160

AC:

AN:

1001550

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

499682

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25866

American (AMR)

AF:

0.00

AC:

AN:

31642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15958

East Asian (EAS)

AF:

0.00

AC:

AN:

30392

South Asian (SAS)

AF:

0.00

AC:

AN:

64570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3080

European-Non Finnish (NFE)

AF:

0.0000185

AC:

AN:

756554

Other (OTH)

AF:

0.0000476

AC:

AN:

41994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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: AC0;AS_VQSR

AF:

0.00

AC:

AN:

96058

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

46286

African (AFR)

AF:

0.00

AC:

AN:

27520

American (AMR)

AF:

0.00

AC:

AN:

8914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2008

East Asian (EAS)

AF:

0.00

AC:

AN:

3602

South Asian (SAS)

AF:

0.00

AC:

AN:

2942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

198

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

43088

Other (OTH)

AF:

0.00

AC:

AN:

1214

Alfa

AF:

0.00

Hom.:

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

0.080

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.046

Eigen

Benign

-0.073

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.63

M_CAP

Benign

0.0051

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-0.98

MutationAssessor

Pathogenic

2.9

PhyloP100

4.0

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.15

Sift

Uncertain

0.022

Sift4G

Benign

0.086

Polyphen

0.85

Vest4

0.66

MutPred

0.71

Gain of sheet (P = 0.1451)

MVP

0.13

MPC

1.9

ClinPred

0.47

GERP RS

1.8

Varity_R

0.17

gMVP

0.75

Mutation Taster

=88/12

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