Variant 2-99578384-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001386135.1(AFF3):c.2861C>G(p.Ser954Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000567 in 1,611,342 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

AFF3
NM_001386135.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.34

Variant links:

Genes affected

AFF3 (HGNC:6473): (ALF transcription elongation factor 3) This gene encodes a tissue-restricted nuclear transcriptional activator that is preferentially expressed in lymphoid tissue. Isolation of this protein initially defined a highly conserved LAF4/MLLT2 gene family of nuclear transcription factors that may function in lymphoid development and oncogenesis. In some ALL patients, this gene has been found fused to the gene for MLL. Multiple alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Jul 2008]

AFF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010810375).

BP6

Variant 2-99578384-G-C is Benign according to our data. Variant chr2-99578384-G-C is described in ClinVar as [Benign]. Clinvar id is 2651184.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 455 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFF3	NM_001386135.1 linkuse as main transcript	c.2861C>G	p.Ser954Cys	missense_variant	18/25	ENST00000672756.2	NP_001373064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFF3	ENST00000672756.2 linkuse as main transcript	c.2861C>G	p.Ser954Cys	missense_variant	18/25		NM_001386135.1	ENSP00000500419	A2	P51826-1

Frequencies

GnomAD3 genomes

AF:

0.00297

AC:

452

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

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:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000765

AC:

190

AN:

248284

Hom.:

AF XY:

0.000641

AC XY:

AN XY:

134206

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.000542

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.000667

GnomAD4 exome

AF:

0.000314

AC:

458

AN:

1459006

Hom.:

Cov.:

AF XY:

0.000276

AC XY:

200

AN XY:

725708

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.000630

GnomAD4 genome

AF:

0.00299

AC:

455

AN:

152336

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

228

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0103

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000417

Hom.:

Bravo

AF:

0.00341

ESP6500AA

AF:

0.00976

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000964

AC:

117

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

AFF3: BP4, BS1, BS2 -

AFF3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 18, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

.;T;T

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Uncertain

-0.13

MutationAssessor

Pathogenic

3.0

M;M;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.048

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.57

MVP

0.57

ClinPred

0.026

GERP RS

5.3

Varity_R

0.15

gMVP

0.50

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