Variant X-93709788-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_001171109.2(FAM133A):c.369G>C(p.Glu123Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 1,192,525 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 103 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., 40 hem., cov: 22)

Exomes 𝑓: 0.00015 ( 0 hom. 63 hem. )

Consequence

FAM133A
NM_001171109.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

FAM133A (HGNC:26748): (family with sequence similarity 133 member A)

FAM133A 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=0.005131662).

BP6

Variant X-93709788-G-C is Benign according to our data. Variant chrX-93709788-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 728790.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-93709788-G-C is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 40 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM133A	NM_001171109.2 linkuse as main transcript	c.369G>C	p.Glu123Asp	missense_variant	4/4	ENST00000683942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAM133A	ENST00000683942.1 linkuse as main transcript	c.369G>C	p.Glu123Asp	missense_variant	4/4		NM_001171109.2	P1
FAM133A	ENST00000322139.4 linkuse as main transcript	c.369G>C	p.Glu123Asp	missense_variant	3/3	4		P1
FAM133A	ENST00000332647.5 linkuse as main transcript	c.369G>C	p.Glu123Asp	missense_variant	4/4	2		P1

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

157

AN:

110893

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

33251

show subpopulations

Gnomad AFR

AF:

0.00481

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000771

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:

0.0000189

Gnomad OTH

AF:

0.000671

GnomAD3 exomes

AF:

0.000523

AC:

AN:

151164

Hom.:

AF XY:

0.000240

AC XY:

AN XY:

45806

show subpopulations

Gnomad AFR exome

AF:

0.00596

Gnomad AMR exome

AF:

0.000535

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:

0.0000782

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000152

AC:

164

AN:

1081587

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

351653

show subpopulations

Gnomad4 AFR exome

AF:

0.00457

Gnomad4 AMR exome

AF:

0.000514

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:

0.0000120

Gnomad4 OTH exome

AF:

0.000352

GnomAD4 genome

AF:

0.00142

AC:

157

AN:

110938

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

33306

show subpopulations

Gnomad4 AFR

AF:

0.00480

Gnomad4 AMR

AF:

0.000770

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.000663

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.00179

ESP6500AA

AF:

0.00472

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000535

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

Invitae

Nov 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.028

T;T

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.65

T;.

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.099

Sift

Benign

0.20

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.83

P;P

Vest4

0.16

MutPred

0.12

Gain of MoRF binding (P = 0.0896);Gain of MoRF binding (P = 0.0896);

MVP

0.068

ClinPred

0.029

GERP RS

0.63

Varity_R

0.12

gMVP

0.0046

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