Genetic Variant FAM86B1:p.Glu262Lys (chr8-12185382-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001083537.4(FAM86B1):c.784G>A(p.Glu262Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000031 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B1
NM_001083537.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.788

Variant links:

Genes affected

FAM86B1 (HGNC:28268): (family with sequence similarity 86 member B1) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. [provided by Alliance of Genome Resources, Apr 2022]

FAM86B1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B1	NM_001083537.4 link	c.784G>A	p.Glu262Lys	missense_variant	Exon 6 of 7	ENST00000448228.7	NP_001077006.1	Q8N7N1-1Q4KMP3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B1	ENST00000448228.7 link	c.784G>A	p.Glu262Lys	missense_variant	Exon 6 of 7	5	NM_001083537.4	ENSP00000407067.2		Q8N7N1-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148564

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000246

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000377

AC:

AN:

238698

Hom.:

AF XY:

0.0000462

AC XY:

AN XY:

129964

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000584

Gnomad SAS exome

AF:

0.0000679

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000368

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000306

AC:

AN:

1439532

Hom.:

Cov.:

AF XY:

0.0000349

AC XY:

AN XY:

715904

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000786

Gnomad4 SAS exome

AF:

0.0000359

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000291

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000135

AC:

AN:

148564

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72406

show subpopulations

Gnomad4 AFR

AF:

0.0000246

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000966

Hom.:

ExAC

AF:

0.0000256

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.784G>A (p.E262K) alteration is located in exon 6 (coding exon 6) of the FAM86B1 gene. This alteration results from a G to A substitution at nucleotide position 784, causing the glutamic acid (E) at amino acid position 262 to be replaced by a lysine (K). 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

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.0038

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.12

Sift

Benign

0.19

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0020

B;B

Vest4

0.47

MutPred

0.57

.;Gain of ubiquitination at E296 (P = 0.0325);

MVP

0.068

MPC

2.0

ClinPred

0.051

GERP RS

1.2

Varity_R

0.052

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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