Genetic Variant FAM86B2:p.Ala275Pro (chr8-12427726-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001137610.3(FAM86B2):c.823G>C(p.Ala275Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 13)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B2
NM_001137610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0780

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2822862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3 link	c.823G>C	p.Ala275Pro	missense_variant	Exon 7 of 8	ENST00000262365.9	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2 link	n.512G>C		non_coding_transcript_exon_variant	Exon 5 of 6
FAM86B2	NR_148877.2 link	n.431G>C		non_coding_transcript_exon_variant	Exon 4 of 5
FAM86B2	NR_148878.2 link	n.712G>C		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B2	ENST00000262365.9 link	c.823G>C	p.Ala275Pro	missense_variant	Exon 7 of 8	5	NM_001137610.3	ENSP00000262365.4		P0C5J1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000608

AC:

AN:

164564

Hom.:

AF XY:

0.00

AC XY:

AN XY:

91010

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000700

Gnomad SAS 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:

0.00000300

AC:

AN:

1000000

Hom.:

Cov.:

AF XY:

0.00000200

AC XY:

AN XY:

498968

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000987

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.823G>C (p.A275P) alteration is located in exon 7 (coding exon 7) of the FAM86B2 gene. This alteration results from a G to C substitution at nucleotide position 823, causing the alanine (A) at amino acid position 275 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.6

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0051

T;T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

L;.;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.6

N;.;N

REVEL

Benign

0.035

Sift

Benign

0.18

T;.;T

Sift4G

Benign

0.18

T;D;T

Polyphen

0.020

B;.;.

Vest4

0.21

MutPred

0.46

Gain of sheet (P = 0.0101);.;.;

MVP

0.082

MPC

3.3

ClinPred

0.074

GERP RS

0.60

Varity_R

0.12

gMVP

0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over