Variant chr15-59514336-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152450.3(FAM81A):c.698G>A(p.Arg233Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000276 in 1,613,338 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

FAM81A
NM_152450.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

Variant links:

Genes affected

FAM81A (HGNC:28379): (family with sequence similarity 81 member A)

FAM81A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM81A	NM_152450.3 linkuse as main transcript	c.698G>A	p.Arg233Gln	missense_variant	7/9	ENST00000288228.10	NP_689663.2	Q8TBF8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM81A	ENST00000288228.10 linkuse as main transcript	c.698G>A	p.Arg233Gln	missense_variant	7/9	1	NM_152450.3	ENSP00000288228.5		Q8TBF8

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

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:

0.0000950

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000125

AC:

AN:

248876

Hom.:

AF XY:

0.0000666

AC XY:

AN XY:

135034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000231

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000291

AC:

425

AN:

1461402

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

191

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000359

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000132

AC:

AN:

151936

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000950

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000492

AC:

ExAC

AF:

0.000108

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

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

Dec 13, 2022

The c.698G>A (p.R233Q) alteration is located in exon 7 (coding exon 6) of the FAM81A gene. This alteration results from a G to A substitution at nucleotide position 698, causing the arginine (R) at amino acid position 233 to be replaced by a glutamine (Q). 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

-0.026

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.042

Eigen

Uncertain

0.62

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.063

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.67

REVEL

Uncertain

0.33

Sift

Benign

0.63

Sift4G

Benign

0.53

Polyphen

1.0

Vest4

0.76

MVP

0.71

MPC

0.99

ClinPred

0.31

GERP RS

5.8

Varity_R

0.17

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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