dbSNP rs1408792631: FAM86B2:p.Thr295Pro (chr8-12427666-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001137610.3(FAM86B2):c.883A>C(p.Thr295Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 16 hom., cov: 15)

Exomes 𝑓: 0.0000020 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B2
NM_001137610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.675

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076643527).

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>C	p.Thr295Pro	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2		n.572A>C		non_coding_transcript_exon	Exon 5 of 6
FAM86B2	NR_148877.2		n.491A>C		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>C	p.Thr295Pro	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
FAM86B2	ENST00000942450.1		c.853A>C	p.Thr285Pro	missense	Exon 7 of 8	ENSP00000612509.1
FAM86B2	ENST00000870195.1		c.781A>C	p.Thr261Pro	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

98806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0714

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:

0.0000684

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000200

AC:

AN:

1002458

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

500118

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25848

American (AMR)

AF:

0.00

AC:

AN:

31628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15948

East Asian (EAS)

AF:

0.00

AC:

AN:

30398

South Asian (SAS)

AF:

0.00

AC:

AN:

64634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32018

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3114

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

756868

Other (OTH)

AF:

0.0000476

AC:

AN:

42002

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000486

AC:

AN:

98806

Hom.:

Cov.:

AF XY:

0.000712

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:

0.0000684

AC:

AN:

43890

Other (OTH)

AF:

0.00

AC:

AN:

1256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

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

0.16

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.022

Eigen

Benign

-0.72

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.73

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

PhyloP100

0.68

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.076

Sift

Benign

0.051

Sift4G

Benign

0.14

Polyphen

0.77

Vest4

0.41

MutPred

0.59

Gain of phosphorylation at T294 (P = 0.0621)

MVP

0.10

MPC

3.3

ClinPred

0.28

GERP RS

-2.3

Varity_R

0.26

gMVP

0.65

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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