Variant X-55161143-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001166701.4(VCF2):c.14C>G(p.Pro5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000064 in 1,094,454 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000064 ( 0 hom. 1 hem. )

Consequence

VCF2
NM_001166701.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.65

Variant links:

Genes affected

VCF2 (HGNC:25085): (VCP nuclear cofactor family member 2)

VCF2 links:

VCF2 (HGNC:):

VCF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07610276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCF2	NM_001166701.4 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/3	ENST00000685693.1	NP_001160173.1	A0A8I5KUH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM104B	ENST00000685693.1 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/3		NM_001166701.4	ENSP00000509111.1		A0A8I5KUH0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000175

AC:

AN:

171523

Hom.:

AF XY:

0.0000343

AC XY:

AN XY:

58329

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000225

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:

0.00000640

AC:

AN:

1094454

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

360350

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000665

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000595

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Jan 31, 2024

The c.14C>G (p.P5R) alteration is located in exon 1 (coding exon 1) of the FAM104B gene. This alteration results from a C to G substitution at nucleotide position 14, causing the proline (P) at amino acid position 5 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

0.17

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.99

CADD

Benign

8.0

DANN

Benign

0.96

DEOGEN2

Benign

0.0010

.;T;.;.

FATHMM_MKL

Benign

0.0058

LIST_S2

Benign

0.50

T;T;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.076

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

1.1

N;N;N;D

REVEL

Benign

0.017

Sift

Uncertain

0.0040

D;D;T;D

Sift4G

Benign

0.98

T;T;T;D

Polyphen

0.0060

B;B;B;.

Vest4

0.13

MutPred

0.36

Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);

MVP

0.27

MPC

0.46

ClinPred

0.046

GERP RS

-2.2

Varity_R

0.061

gMVP

0.038

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