Variant X-55160865-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001166701.4(FAM104B):c.20+272T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000606 in 1,154,627 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000057 ( 0 hom. 2 hem. )

Consequence

FAM104B
NM_001166701.4 intron

Scores

Splicing: ADA: 0.00005583

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: -0.256

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059637368).

BP6

Variant X-55160865-A-G is Benign according to our data. Variant chrX-55160865-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1328346.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-55160865-A-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM104B	NM_001166701.4 linkuse as main transcript	c.20+272T>C		intron_variant		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.20+272T>C		intron_variant			NM_001166701.4	ENSP00000509111	A2

Frequencies

GnomAD3 genomes

AF:

0.00000902

AC:

AN:

110869

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

33105

show subpopulations

Gnomad AFR

AF:

0.0000329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00000977

AC:

AN:

102348

Hom.:

AF XY:

0.00

AC XY:

AN XY:

37396

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:

0.0000704

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000575

AC:

AN:

1043708

Hom.:

Cov.:

AF XY:

0.00000585

AC XY:

AN XY:

341772

show subpopulations

Gnomad4 AFR exome

AF:

0.0000803

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:

0.00000122

Gnomad4 OTH exome

AF:

0.0000677

GnomAD4 genome

AF:

0.00000902

AC:

AN:

110919

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

33165

show subpopulations

Gnomad4 AFR

AF:

0.0000329

Gnomad4 AMR

AF:

0.00

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

Bravo

AF:

0.00000756

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-1.1

CADD

Benign

2.1

DANN

Benign

0.76

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.23

M_CAP

Benign

0.0031

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N

PROVEAN

Benign

0.13

REVEL

Benign

0.042

Sift

Benign

0.047

Sift4G

Uncertain

0.0080

Vest4

0.18

MutPred

0.38

Gain of phosphorylation at L6 (P = 0.0341);

MVP

0.030

ClinPred

0.024

GERP RS

-2.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000056

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.060

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