Variant 17-73232258-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001098832.2(FAM104A):c.49A>C(p.Thr17Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,610,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FAM104A
NM_001098832.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.676

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06514457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FAM104A	NM_001098832.2 linkuse as main transcript	c.49A>C	p.Thr17Pro	missense_variant	1/4	ENST00000405159.8	NP_001092302.1
FAM104A	NM_032837.3 linkuse as main transcript	c.49A>C	p.Thr17Pro	missense_variant	1/3		NP_116226.2
FAM104A	NM_001289411.1 linkuse as main transcript	c.49A>C	p.Thr17Pro	missense_variant	1/3		NP_001276340.1
FAM104A	NM_001289410.1 linkuse as main transcript	c.49A>C	p.Thr17Pro	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.49A>C	p.Thr17Pro	missense_variant	1/4	1	NM_001098832.2	ENSP00000384832		Q969W3-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458822

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725546

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

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: 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

Dec 06, 2022

The c.49A>C (p.T17P) alteration is located in exon 1 (coding exon 1) of the FAM104A gene. This alteration results from a A to C substitution at nucleotide position 49, causing the threonine (T) at amino acid position 17 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

0.067

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.018

T;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.49

T;T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.065

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.46

N;N;.;.

REVEL

Benign

0.034

Sift

Benign

0.15

T;T;.;.

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.0010

B;B;.;.

Vest4

0.21

MutPred

0.15

Loss of phosphorylation at T17 (P = 0.013);Loss of phosphorylation at T17 (P = 0.013);Loss of phosphorylation at T17 (P = 0.013);Loss of phosphorylation at T17 (P = 0.013);

MVP

0.33

MPC

0.17

ClinPred

0.035

GERP RS

-0.18

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.10

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