chrX-154486574-G-A

Variant names:

• chrX-154486574-G-A
• rs1557212992
• NM_014235.5:c.11C>T

Variant summary

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

The NM_014235.5(UBL4A):​c.11C>T​(p.Thr4Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. T4K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000093 (0 hom., 1 hem., cov: 20)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: UBL4A NM_014235.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• 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 0 ACMG points.

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.11C>T	p.Thr4Met	missense	Exon 1 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.11C>T	p.Thr4Met	missense	Exon 1 of 4	ENSP00000358674.4	P11441
	UBL4A	ENST00000369653.8	TSL:3	c.11C>T	p.Thr4Met	missense	Exon 1 of 5	ENSP00000358667.4	Q5HY81
	UBL4A	ENST00000630530.1	TSL:5	c.11C>T	p.Thr4Met	missense	Exon 1 of 2	ENSP00000486867.1	F8WCT8

Frequencies

GnomAD3 genomes AF: 0.00000932 AC: 1 AN: 107290 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.00 AC: 0 AN: 30578 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 862732 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 264464

African (AFR) AF: 0.00 AC: 0 AN: 17071

American (AMR) AF: 0.00 AC: 0 AN: 12470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12297

East Asian (EAS) AF: 0.00 AC: 0 AN: 15981

South Asian (SAS) AF: 0.00 AC: 0 AN: 29244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2096

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 720771

Other (OTH) AF: 0.00 AC: 0 AN: 33598

GnomAD4 genome AF: 0.00000932 AC: 1 AN: 107290 Hom.: 0 Cov.: 20 AF XY: 0.0000322 AC XY: 1 AN XY: 31014

African (AFR) AF: 0.0000335 AC: 1 AN: 29863

American (AMR) AF: 0.00 AC: 0 AN: 10348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2594

East Asian (EAS) AF: 0.00 AC: 0 AN: 3339

South Asian (SAS) AF: 0.00 AC: 0 AN: 2631

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 229

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51325

Other (OTH) AF: 0.00 AC: 0 AN: 1441

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.86	D
M_CAP	Pathogenic	0.89	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.22
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.41		Gain of methylation at K6 (P = 0.0553)
MVP		0.91
MPC		1.3
ClinPred		0.98	D
GERP RS		4.0
PromoterAI		-0.053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.48
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs1557212992; hg19: chrX-153714913;