Variant chrX-93710081-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001171109.2(FAM133A):c.662A>G(p.Lys221Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000342 in 1,198,070 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000025 ( 0 hom. 7 hem. )

Consequence

FAM133A
NM_001171109.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09663072).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM133A	NM_001171109.2 linkuse as main transcript	c.662A>G	p.Lys221Arg	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.662A>G	p.Lys221Arg	missense_variant	4/4		NM_001171109.2	P1
FAM133A	ENST00000322139.4 linkuse as main transcript	c.662A>G	p.Lys221Arg	missense_variant	3/3	4		P1
FAM133A	ENST00000332647.5 linkuse as main transcript	c.662A>G	p.Lys221Arg	missense_variant	4/4	2		P1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

111595

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

33805

show subpopulations

Gnomad AFR

AF:

0.000390

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000192

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000178

AC:

AN:

168759

Hom.:

AF XY:

0.0000176

AC XY:

AN XY:

56837

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000249

AC:

AN:

1086427

Hom.:

Cov.:

AF XY:

0.0000198

AC XY:

AN XY:

353363

show subpopulations

Gnomad4 AFR exome

AF:

0.000967

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000439

GnomAD4 genome

AF:

0.000125

AC:

AN:

111643

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33863

show subpopulations

Gnomad4 AFR

AF:

0.000389

Gnomad4 AMR

AF:

0.000191

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000189

ExAC

AF:

0.0000248

AC:

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

May 27, 2022

The c.662A>G (p.K221R) alteration is located in exon 5 (coding exon 1) of the FAM133A gene. This alteration results from a A to G substitution at nucleotide position 662, causing the lysine (K) at amino acid position 221 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

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0083

T;T

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.43

T;.

M_CAP

Benign

0.038

MetaRNN

Benign

0.097

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.086

Sift

Benign

0.065

T;T

Sift4G

Uncertain

0.037

D;D

Polyphen

1.0

D;D

Vest4

0.19

MVP

0.22

ClinPred

0.17

GERP RS

2.8

Varity_R

0.084

gMVP

0.0019

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