Variant 17-73232296-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001098832.2(FAM104A):c.11G>C(p.Arg4Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000767 in 1,435,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

FAM104A
NM_001098832.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

Variant links:

Genes affected

FAM104A (HGNC:25918): (VCP nuclear cofactor family member 1)

FAM104A links:

C17orf80 (HGNC:29601): (mitochondrial nucleoid associated protein 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

C17orf80 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a modified_residue Omega-N-methylarginine (size 0) in uniprot entity F104A_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FAM104A	NM_001098832.2 linkuse as main transcript	c.11G>C	p.Arg4Pro	missense_variant	1/4	ENST00000405159.8	NP_001092302.1
FAM104A	NM_032837.3 linkuse as main transcript	c.11G>C	p.Arg4Pro	missense_variant	1/3		NP_116226.2
FAM104A	NM_001289411.1 linkuse as main transcript	c.11G>C	p.Arg4Pro	missense_variant	1/3		NP_001276340.1
FAM104A	NM_001289410.1 linkuse as main transcript	c.11G>C	p.Arg4Pro	missense_variant	1/2		NP_001276339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM104A	ENST00000405159.8 linkuse as main transcript	c.11G>C	p.Arg4Pro	missense_variant	1/4	1	NM_001098832.2	ENSP00000384832		Q969W3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000133

AC:

AN:

226270

Hom.:

AF XY:

0.0000160

AC XY:

AN XY:

124726

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:

0.0000298

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000767

AC:

AN:

1435026

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

710432

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000913

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

ExAC

AF:

0.0000166

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

Mar 22, 2022

The c.11G>C (p.R4P) alteration is located in exon 1 (coding exon 1) of the FAM104A gene. This alteration results from a G to C substitution at nucleotide position 11, causing the arginine (R) at amino acid position 4 to be replaced by a proline (P). 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

0.29

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;.;.;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.81

T;T;T;T

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.90

L;L;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.52

N;N;.;.

REVEL

Benign

0.21

Sift

Uncertain

0.014

D;D;.;.

Sift4G

Uncertain

0.050

T;T;T;T

Polyphen

1.0

D;D;.;.

Vest4

0.72

MutPred

0.31

Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);

MVP

0.61

MPC

0.18

ClinPred

0.67

GERP RS

4.9

Varity_R

0.33

gMVP

0.33

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