Genetic Variant FAM86B1:p.Pro253Arg (chr8-12185408-G-C) – 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.758C>G(p.Pro253Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 6 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B1
NM_001083537.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

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.758C>G	p.Pro253Arg	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.758C>G	p.Pro253Arg	missense_variant	Exon 6 of 7	5	NM_001083537.4	ENSP00000407067.2		Q8N7N1-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148506

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000547

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:

0.0000898

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000657

AC:

AN:

228478

Hom.:

AF XY:

0.0000723

AC XY:

AN XY:

124548

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000227

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:

0.0000665

Gnomad OTH exome

AF:

0.000177

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000100

AC:

144

AN:

1440060

Hom.:

Cov.:

AF XY:

0.0000922

AC XY:

AN XY:

716160

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000138

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.0000504

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000101

AC:

AN:

148506

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

72376

show subpopulations

Gnomad4 AFR

AF:

0.0000246

Gnomad4 AMR

AF:

0.000547

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000898

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000193

Hom.:

ExAC

AF:

0.0000690

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.758C>G (p.P253R) alteration is located in exon 6 (coding exon 6) of the FAM86B1 gene. This alteration results from a C to G substitution at nucleotide position 758, causing the proline (P) at amino acid position 253 to be replaced by an arginine (R). 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

0.089

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0059

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Benign

0.090

Sift

Uncertain

0.022

D;D

Sift4G

Uncertain

0.022

D;D

Polyphen

0.062

B;B

Vest4

0.55

MVP

0.082

MPC

2.0

ClinPred

0.12

GERP RS

1.2

Varity_R

0.23

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