16-4609713-C-T

Variant names:

• chr16-4609713-C-T
• NM_145253.3:c.454G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145253.3(UBALD1):​c.454G>A​(p.Ala152Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBALD1 NM_145253.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.510
• Publications: 0 publications found

Genes affected

UBALD1 (HGNC:29576): (UBA like domain containing 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02626744).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145253.3. 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
	UBALD1	NM_145253.3	MANE Select	c.454G>A	p.Ala152Thr	missense	Exon 3 of 3	NP_660296.1	Q8TB05-1
	UBALD1	NM_001330467.2		c.379G>A	p.Ala127Thr	missense	Exon 3 of 3	NP_001317396.1	K7EM88
	UBALD1	NM_001411032.1		c.*270G>A		3_prime_UTR	Exon 3 of 3	NP_001397961.1	K7EKR5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBALD1	ENST00000283474.12	TSL:1 MANE Select	c.454G>A	p.Ala152Thr	missense	Exon 3 of 3	ENSP00000283474.6	Q8TB05-1
	UBALD1	ENST00000590891.1	TSL:6	c.559G>A	p.Ala187Thr	missense	Exon 1 of 1	ENSP00000465706.1	Q8TB05-2
	UBALD1	ENST00000591401.5	TSL:5	c.391G>A	p.Ala131Thr	missense	Exon 2 of 2	ENSP00000467671.1	K7EQ49

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1323128 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 646532

African (AFR) AF: 0.00 AC: 0 AN: 27672

American (AMR) AF: 0.00 AC: 0 AN: 24602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18592

East Asian (EAS) AF: 0.00 AC: 0 AN: 35176

South Asian (SAS) AF: 0.00 AC: 0 AN: 65024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4540

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1046528

Other (OTH) AF: 0.00 AC: 0 AN: 54112

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.51
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.065
Sift	Benign	1.0	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.061
MutPred		0.18		Gain of glycosylation at A152 (P = 0.0019)
MVP		0.11
MPC		0.16
ClinPred		0.20	T
GERP RS		-0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.15

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

hg19: chr16-4659714; COSMIC: COSV105109464; COSMIC: COSV105109464;