X-154485824-C-G

Variant names:

• chrX-154485824-C-G
• rs377663564
• NM_014235.5:c.310G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014235.5(UBL4A):​c.310G>C​(p.Ala104Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A104S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.3e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: UBL4A NM_014235.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 0 publications found

Genes affected

UBL4A (HGNC:12505): (ubiquitin like 4A) Enables chaperone binding activity. Involved in tail-anchored membrane protein insertion into ER membrane. Located in cytosol; membrane; and nucleoplasm. Part of BAT3 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014235.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBL4A	NM_014235.5	MANE Select	c.310G>C	p.Ala104Pro	missense	Exon 3 of 4	NP_055050.1	P11441

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBL4A	ENST00000369660.9	TSL:1 MANE Select	c.310G>C	p.Ala104Pro	missense	Exon 3 of 4	ENSP00000358674.4	P11441
	UBL4A	ENST00000369653.8	TSL:3	c.310G>C	p.Ala104Pro	missense	Exon 3 of 5	ENSP00000358667.4	Q5HY81
	UBL4A	ENST00000417913.1	TSL:5	n.*102G>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000397223.1	F8WB70

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000633 AC: 1 AN: 158093 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000144

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.28e-7 AC: 1 AN: 1078150 Hom.: 0 Cov.: 32 AF XY: 0.00000284 AC XY: 1 AN XY: 352250

African (AFR) AF: 0.00 AC: 0 AN: 26235

American (AMR) AF: 0.00 AC: 0 AN: 34131

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30146

South Asian (SAS) AF: 0.00 AC: 0 AN: 49694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38727

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3878

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 832582

Other (OTH) AF: 0.00 AC: 0 AN: 45374

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000331 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.18
Sift	Benign	0.050	D
Sift4G	Benign	0.25	T
Polyphen		0.86	P
Vest4		0.56
MutPred		0.39		Gain of loop (P = 0.0195)
MVP		0.99
MPC		1.3
ClinPred		0.73	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.96
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs377663564; hg19: chrX-153714163;