Genetic Variant FAM86B2:p.Thr295Ala (chr8-12427666-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001137610.3(FAM86B2):c.883A>G(p.Thr295Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. T295P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 15)

Failed GnomAD Quality Control

Consequence

FAM86B2
NM_001137610.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.675

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06854272).

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.883A>G	p.Thr295Ala	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2		n.572A>G		non_coding_transcript_exon	Exon 5 of 6
FAM86B2	NR_148877.2		n.491A>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.883A>G	p.Thr295Ala	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
FAM86B2	ENST00000942450.1		c.853A>G	p.Thr285Ala	missense	Exon 7 of 8	ENSP00000612509.1
FAM86B2	ENST00000870195.1		c.781A>G	p.Thr261Ala	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes

AF:

0.0000202

AC:

AN:

98806

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:

0.0000456

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000202

AC:

AN:

98806

Hom.:

Cov.:

AF XY:

0.0000210

AC XY:

AN XY:

47728

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28836

American (AMR)

AF:

0.00

AC:

AN:

9150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2038

East Asian (EAS)

AF:

0.00

AC:

AN:

3650

South Asian (SAS)

AF:

0.00

AC:

AN:

3054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.0000456

AC:

AN:

43890

Other (OTH)

AF:

0.00

AC:

AN:

1256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.0

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0049

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.55

M_CAP

Benign

0.0043

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.35

PhyloP100

0.68

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.3

REVEL

Benign

0.028

Sift

Benign

0.38

Sift4G

Benign

0.63

Polyphen

0.0020

Vest4

0.099

MutPred

0.51

Gain of helix (P = 0.2059)

MVP

0.043

MPC

1.8

ClinPred

0.035

GERP RS

-2.3

Varity_R

0.029

gMVP

0.27

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