16-4609832-G-A

Variant names:

• chr16-4609832-G-A
• rs781647475
• NM_145253.3:c.335C>T

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.335C>T​(p.Pro112Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. P112R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: UBALD1 NM_145253.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• 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=0.19523779).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBALD1	NM_145253.3	c.335C>T	p.Pro112Leu	missense_variant	Exon 3 of 3	ENST00000283474.12	NP_660296.1
UBALD1	NM_001330467.2	c.260C>T	p.Pro87Leu	missense_variant	Exon 3 of 3		NP_001317396.1
UBALD1	NM_001411032.1	c.*151C>T		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.335C>T	p.Pro112Leu	missense_variant	Exon 3 of 3	1	NM_145253.3	ENSP00000283474.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1380632 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 678818

African (AFR) AF: 0.00 AC: 0 AN: 31042

American (AMR) AF: 0.00 AC: 0 AN: 33100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21120

East Asian (EAS) AF: 0.00 AC: 0 AN: 38322

South Asian (SAS) AF: 0.00 AC: 0 AN: 74960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5374

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1072224

Other (OTH) AF: 0.00 AC: 0 AN: 56726

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0056	.;.;T;T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.84	T;T;T;T;D;D
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;.;L;.;.;.
PhyloP100		3.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	.;.;N;.;.;.
REVEL	Benign	0.086
Sift	Uncertain	0.014	.;.;D;.;.;.
Sift4G	Uncertain	0.0020	D;D;D;D;D;D
Polyphen		0.21, 0.43	.;.;B;B;.;.
Vest4		0.27
MutPred		0.26		.;.;Loss of loop (P = 0.0128);.;.;.;
MVP		0.17
MPC		0.16
ClinPred		0.62	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.34
Mutation Taster		=75/25	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: rs781647475; hg19: chr16-4659833; COSMIC: COSV108051416;