Variant X-55143826-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001166701.4(VCF2):c.*2258G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,206,382 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., 13 hem., cov: 22)

Exomes 𝑓: 0.000064 ( 0 hom. 29 hem. )

Consequence

VCF2
NM_001166701.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10

Variant links:

Genes affected

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

FAM104B links:

VCF2 (HGNC:):

VCF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCF2	NM_001166701.4 linkuse as main transcript	c.*2258G>A		3_prime_UTR_variant	3/3	ENST00000685693.1	NP_001160173.1	A0A8I5KUH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM104B	ENST00000332132.8 linkuse as main transcript	c.304G>A	p.Glu102Lys	missense_variant	4/4	1		ENSP00000333394.4	Q5XKR9-2
FAM104B	ENST00000358460.8 linkuse as main transcript	c.301G>A	p.Glu101Lys	missense_variant	4/4	1		ENSP00000364101.3	Q5XKR9-1
FAM104B	ENST00000685693 linkuse as main transcript	c.*2258G>A		3_prime_UTR_variant	3/3		NM_001166701.4	ENSP00000509111.1	A0A8I5KUH0

Frequencies

GnomAD3 genomes

AF:

0.000503

AC:

AN:

111337

Hom.:

Cov.:

AF XY:

0.000358

AC XY:

AN XY:

33541

show subpopulations

Gnomad AFR

AF:

0.00170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000287

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000375

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000165

AC:

AN:

182134

Hom.:

AF XY:

0.000135

AC XY:

AN XY:

66634

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.0000369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000373

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000639

AC:

AN:

1094993

Hom.:

Cov.:

AF XY:

0.0000804

AC XY:

AN XY:

360671

show subpopulations

Gnomad4 AFR exome

AF:

0.00133

Gnomad4 AMR exome

AF:

0.0000569

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000354

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000283

GnomAD4 genome

AF:

0.000512

AC:

AN:

111389

Hom.:

Cov.:

AF XY:

0.000387

AC XY:

AN XY:

33603

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.000287

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000376

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000482

Hom.:

Bravo

AF:

0.000438

ESP6500AA

AF:

0.00183

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000231

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

Nov 21, 2023

The c.304G>A (p.E102K) alteration is located in exon 4 (coding exon 4) of the FAM104B gene. This alteration results from a G to A substitution at nucleotide position 304, causing the glutamic acid (E) at amino acid position 102 to be replaced by a lysine (K). 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

0.21

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.9

DANN

Uncertain

0.98

DEOGEN2

Benign

0.020

.;T

FATHMM_MKL

Benign

0.00072

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0076

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.072

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.018

B;P

Vest4

0.15

MVP

0.25

ClinPred

0.036

GERP RS

-2.5

Varity_R

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.33

Position offset: 49

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