16-4609778-G-T

Variant names:

• chr16-4609778-G-T
• rs749015969
• NM_145253.3:c.389C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145253.3(UBALD1):​c.389C>A​(p.Pro130His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: UBALD1 NM_145253.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17898983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBALD1	NM_145253.3	c.389C>A	p.Pro130His	missense_variant	Exon 3 of 3	ENST00000283474.12	NP_660296.1
UBALD1	NM_001330467.2	c.314C>A	p.Pro105His	missense_variant	Exon 3 of 3		NP_001317396.1
UBALD1	NM_001411032.1	c.*205C>A		3_prime_UTR_variant	Exon 3 of 3		NP_001397961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBALD1	ENST00000283474.12	c.389C>A	p.Pro130His	missense_variant	Exon 3 of 3	1	NM_145253.3	ENSP00000283474.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356540 Hom.: 0 Cov.: 32 AF XY: 0.00000150 AC XY: 1 AN XY: 664888

African (AFR) AF: 0.00 AC: 0 AN: 29666

American (AMR) AF: 0.00 AC: 0 AN: 28296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19626

East Asian (EAS) AF: 0.00 AC: 0 AN: 37730

South Asian (SAS) AF: 0.00 AC: 0 AN: 70332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5002

European-Non Finnish (NFE) AF: 9.40e-7 AC: 1 AN: 1064080

Other (OTH) AF: 0.00 AC: 0 AN: 55600

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.389C>A (p.P130H) alteration is located in exon 3 (coding exon 3) of the UBALD1 gene. This alteration results from a C to A substitution at nucleotide position 389, causing the proline (P) at amino acid position 130 to be replaced by a histidine (H). 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	0.10
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.093	.;.;T;T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.047
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.77	T;T;T;T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.9	.;.;L;.;.
PhyloP100		1.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.3	.;.;D;.;.
REVEL	Benign	0.061
Sift	Pathogenic	0.0	.;.;D;.;.
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		0.0090, 0.025	.;.;B;B;.
Vest4		0.21
MVP		0.15
MPC		0.19
ClinPred		0.91	D
GERP RS		4.1
Varity_R		0.35
gMVP		0.35

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: rs749015969; hg19: chr16-4659779;