Variant X-148962726-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBS1BS2

The NM_002025.4(AFF2):c.2702C>T(p.Ser901Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,092,925 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 8 hem. )

Consequence

AFF2
NM_002025.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.62

Variant links:

Genes affected

AFF2 (HGNC:3776): (ALF transcription elongation factor 2) This gene encodes a putative transcriptional activator that is a member of the AF4\FMR2 gene family. This gene is associated with the folate-sensitive fragile X E locus on chromosome X. A repeat polymorphism in the fragile X E locus results in silencing of this gene causing Fragile X E syndrome. Fragile X E syndrome is a form of nonsyndromic X-linked cognitive disability. In addition, this gene contains 6-25 GCC repeats that are expanded to >200 repeats in the disease state. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jul 2016]

AFF2 links:

AFF2 (HGNC:):

AFF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2664014).

BP6

Variant X-148962726-C-T is Benign according to our data. Variant chrX-148962726-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3251007.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000128 (14/1092925) while in subpopulation SAS AF= 0.00026 (14/53892). AF 95% confidence interval is 0.000156. There are 0 homozygotes in gnomad4_exome. There are 8 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFF2	NM_002025.4 linkuse as main transcript	c.2702C>T	p.Ser901Phe	missense_variant	13/21	ENST00000370460.7	NP_002016.2	P51816-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFF2	ENST00000370460.7 linkuse as main transcript	c.2702C>T	p.Ser901Phe	missense_variant	13/21	5	NM_002025.4	ENSP00000359489.2		P51816-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000332

AC:

AN:

180795

Hom.:

AF XY:

0.0000609

AC XY:

AN XY:

65669

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000320

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1092925

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

358905

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000260

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

AFF2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.76

D;.;.;.

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Pathogenic

0.75

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.7

M;.;.;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.6

D;D;.;D

REVEL

Benign

0.23

Sift

Uncertain

0.020

D;D;.;D

Sift4G

Uncertain

0.029

D;D;D;D

Polyphen

0.99

D;D;D;.

Vest4

0.046

MutPred

0.30

Loss of phosphorylation at S901 (P = 0.0028);.;.;.;

MVP

0.61

MPC

0.64

ClinPred

0.57

GERP RS

5.0

Varity_R

0.33

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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