Genetic Variant FAM86B2:p.Ile212Thr (chr8-12428740-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001137610.3(FAM86B2):c.635T>C(p.Ile212Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 19)

Exomes 𝑓: 0.0000043 ( 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: -0.767

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16377386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3 link	c.635T>C	p.Ile212Thr	missense_variant	Exon 6 of 8	ENST00000262365.9	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2 link	n.431+241T>C		intron_variant	Intron 4 of 5
FAM86B2	NR_148877.2 link	n.350+241T>C		intron_variant	Intron 3 of 4
FAM86B2	NR_148878.2 link	n.631+241T>C		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B2	ENST00000262365.9 link	c.635T>C	p.Ile212Thr	missense_variant	Exon 6 of 8	5	NM_001137610.3	ENSP00000262365.4		P0C5J1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000287

AC:

AN:

139378

Hom.:

AF XY:

0.0000268

AC XY:

AN XY:

74708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000435

AC:

AN:

1149944

Hom.:

Cov.:

AF XY:

0.00000347

AC XY:

AN XY:

575868

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.635T>C (p.I212T) alteration is located in exon 6 (coding exon 6) of the FAM86B2 gene. This alteration results from a T to C substitution at nucleotide position 635, causing the isoleucine (I) at amino acid position 212 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.34

DANN

Benign

0.70

DEOGEN2

Benign

0.0049

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.29

N;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.086

Sift

Benign

0.39

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.0050

B;.

Vest4

0.036

MutPred

0.79

Gain of disorder (P = 0.0078);.;

MVP

0.043

MPC

3.6

ClinPred

0.017

GERP RS

-1.6

Varity_R

0.033

gMVP

0.35

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