NM_014235.5:c.310G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. A104T) 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBL4A	NM_014235.5	c.310G>C	p.Ala104Pro	missense_variant	Exon 3 of 4	ENST00000369660.9	NP_055050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBL4A	ENST00000369660.9	c.310G>C	p.Ala104Pro	missense_variant	Exon 3 of 4	1	NM_014235.5	ENSP00000358674.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000633 AC: 1 AN: 158093 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 54495

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: 0.0000144

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

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: 0.00000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000331 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.18
Sift	Benign	0.050	D;T
Sift4G	Benign	0.25	T;T
Polyphen		0.86	P;.
Vest4		0.56
MutPred		0.39		Gain of loop (P = 0.0195);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs377663564; hg19: chrX-153714163;