Variant X-55146205-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001166701.4(FAM104B):c.227A>C(p.Asn76Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000364 in 1,209,443 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000037 ( 0 hom. 10 hem. )

Consequence

FAM104B
NM_001166701.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: -0.106

Variant links:

Genes affected

FAM104B (HGNC:25085): (VCP nuclear cofactor family member 2)

FAM104B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07323688).

BP6

Variant X-55146205-T-G is Benign according to our data. Variant chrX-55146205-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1206373.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-55146205-T-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM104B	NM_001166701.4 linkuse as main transcript	c.227A>C	p.Asn76Thr	missense_variant	3/3	ENST00000685693.1	NP_001160173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM104B	ENST00000685693.1 linkuse as main transcript	c.227A>C	p.Asn76Thr	missense_variant	3/3		NM_001166701.4	ENSP00000509111	A2

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111433

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33649

show subpopulations

Gnomad AFR

AF:

0.0000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000382

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183411

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67859

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000373

AC:

AN:

1097954

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

363364

show subpopulations

Gnomad4 AFR exome

AF:

0.000909

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000217

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111489

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33715

show subpopulations

Gnomad4 AFR

AF:

0.0000652

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000383

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.6

DANN

Benign

0.92

DEOGEN2

Benign

0.057

.;T;.;.;.

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.66

T;T;T;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.073

T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.7

.;L;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-4.0

D;D;D;D;D

REVEL

Benign

0.027

Sift

Uncertain

0.0030

D;D;T;T;T

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.77

P;P;B;.;.

Vest4

0.22

MVP

0.13

MPC

0.13

ClinPred

0.60

GERP RS

-1.1

Varity_R

0.39

gMVP

0.12

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