Variant 8-12186423-G-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.569C>T(p.Ala190Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000058 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B1
NM_001083537.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.49

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:

FAM85A (HGNC:):

FAM85A 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=0.0076270998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM86B1	NM_001083537.4 linkuse as main transcript	c.569C>T	p.Ala190Val	missense_variant	5/7	ENST00000448228.7
FAM85A	NR_146925.1 linkuse as main transcript	n.688G>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM86B1	ENST00000448228.7 linkuse as main transcript	c.569C>T	p.Ala190Val	missense_variant	5/7	5	NM_001083537.4		Q8N7N1-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148076

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000674

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000617

Gnomad SAS

AF:

0.000216

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000300

Gnomad OTH

AF:

0.000497

GnomAD3 exomes

AF:

0.000183

AC:

AN:

191188

Hom.:

AF XY:

0.000144

AC XY:

AN XY:

104172

show subpopulations

Gnomad AFR exome

AF:

0.00202

Gnomad AMR exome

AF:

0.0000351

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000656

Gnomad SAS exome

AF:

0.000159

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000197

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000577

AC:

AN:

1454904

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

723720

show subpopulations

Gnomad4 AFR exome

AF:

0.00124

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000480

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000526

AC:

AN:

148170

Hom.:

Cov.:

AF XY:

0.000540

AC XY:

AN XY:

72246

show subpopulations

Gnomad4 AFR

AF:

0.00174

Gnomad4 AMR

AF:

0.0000673

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000618

Gnomad4 SAS

AF:

0.000216

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000300

Gnomad4 OTH

AF:

0.000492

Alfa

AF:

0.000759

Hom.:

ExAC

AF:

0.000178

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

Aug 01, 2022

The c.569C>T (p.A190V) alteration is located in exon 5 (coding exon 5) of the FAM86B1 gene. This alteration results from a C to T substitution at nucleotide position 569, causing the alanine (A) at amino acid position 190 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0056

T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0076

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

0.54

D;D;D;D;D

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.065

Sift

Benign

0.32

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.097

B;B

Vest4

0.21

MVP

0.043

MPC

1.9

ClinPred

0.029

GERP RS

1.2

Varity_R

0.14

gMVP

0.31

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