X-55159199-C-A

Position:

• chrX-55159199-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166701.4(FAM104B):​c.50G>T​(p.Gly17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: FAM104B NM_001166701.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.264

Genes affected

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

ACMG classification

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=0.07050228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM104B	NM_001166701.4	c.50G>T	p.Gly17Val	missense_variant	2/3	ENST00000685693.1	NP_001160173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM104B	ENST00000685693.1	c.50G>T	p.Gly17Val	missense_variant	2/3		NM_001166701.4	ENSP00000509111	A2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000183 AC: 2 AN: 1090489 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 356753

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: 0.00000119

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome Cov.: 23

ExAC AF: 0.000264 AC: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.50G>T (p.G17V) alteration is located in exon 2 (coding exon 2) of the FAM104B gene. This alteration results from a G to T substitution at nucleotide position 50, causing the glycine (G) at amino acid position 17 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.2
DANN	Benign	0.22
DEOGEN2	Benign	0.072	.;T;.;.;.;.
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.65	T;T;T;T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.071	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.2	D;D;D;D;N;D
REVEL	Benign	0.060
Sift	Uncertain	0.0080	D;D;D;D;D;D
Sift4G	Uncertain	0.029	D;D;D;D;D;D
Polyphen		0.38	B;B;B;.;.;.
Vest4		0.24
MutPred		0.16		Loss of glycosylation at S14 (P = 0.0895);Loss of glycosylation at S14 (P = 0.0895);Loss of glycosylation at S14 (P = 0.0895);Loss of glycosylation at S14 (P = 0.0895);.;.;
MVP		0.040
MPC		0.25
ClinPred		0.44	T
GERP RS		-1.3
Varity_R		0.19
gMVP		0.097

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

Other links and lift over

dbSNP: rs758818648; hg19: chrX-55185632; COSMIC: COSV59776069;