Variant 8-12185484-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001083537.4(FAM86B1):c.682G>T(p.Val228Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00073 ( 8 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B1
NM_001083537.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041938484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM86B1	NM_001083537.4 linkuse as main transcript	c.682G>T	p.Val228Phe	missense_variant	6/7	ENST00000448228.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM86B1	ENST00000448228.7 linkuse as main transcript	c.682G>T	p.Val228Phe	missense_variant	6/7	5	NM_001083537.4		Q8N7N1-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

142308

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000154

Gnomad AMI

AF:

0.00464

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:

0.000684

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000464

AC:

AN:

135666

Hom.:

AF XY:

0.000432

AC XY:

AN XY:

74078

show subpopulations

Gnomad AFR exome

AF:

0.000390

Gnomad AMR exome

AF:

0.000158

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000111

Gnomad NFE exome

AF:

0.000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000734

AC:

1046

AN:

1425528

Hom.:

Cov.:

AF XY:

0.000758

AC XY:

538

AN XY:

709548

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.000125

Gnomad4 NFE exome

AF:

0.000919

Gnomad4 OTH exome

AF:

0.000441

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000379

AC:

AN:

142308

Hom.:

Cov.:

AF XY:

0.000276

AC XY:

AN XY:

68904

show subpopulations

Gnomad4 AFR

AF:

0.000154

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:

0.000684

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000387

Hom.:

ExAC

AF:

0.000286

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.682G>T (p.V228F) alteration is located in exon 6 (coding exon 6) of the FAM86B1 gene. This alteration results from a G to T substitution at nucleotide position 682, causing the valine (V) at amino acid position 228 to be replaced by a phenylalanine (F). 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

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.46

M_CAP

Benign

0.0089

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.84

MutationTaster

Benign

0.91

D;D;D;D;N

PROVEAN

Benign

-1.4

REVEL

Benign

0.066

Sift

Benign

0.081

Sift4G

Pathogenic

0.0

Vest4

0.43

MutPred

0.36

Loss of disorder (P = 0.0295);

MVP

0.17

ClinPred

0.086

GERP RS

1.2

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