chr16-4609776-G-T

Variant names:

• chr16-4609776-G-T
• rs777309899
• NM_145253.3:c.391C>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.391C>A​(p.Pro131Thr) 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 1,356,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. P131A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: UBALD1 NM_145253.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• 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=0.1074917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBALD1	NM_145253.3	c.391C>A	p.Pro131Thr	missense_variant	Exon 3 of 3	ENST00000283474.12	NP_660296.1
UBALD1	NM_001330467.2	c.316C>A	p.Pro106Thr	missense_variant	Exon 3 of 3		NP_001317396.1
UBALD1	NM_001411032.1	c.*207C>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.391C>A	p.Pro131Thr	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: 1356408 Hom.: 0 Cov.: 32 AF XY: 0.00000150 AC XY: 1 AN XY: 664826

African (AFR) AF: 0.00 AC: 0 AN: 29632

American (AMR) AF: 0.00 AC: 0 AN: 28186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19578

East Asian (EAS) AF: 0.00 AC: 0 AN: 37756

South Asian (SAS) AF: 0.00 AC: 0 AN: 70262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4988

European-Non Finnish (NFE) AF: 9.40e-7 AC: 1 AN: 1064092

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.091
DEOGEN2	Benign	0.0056	.;.;T;T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T;T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;.;L;.;.
PhyloP100		2.3
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.2	.;.;N;.;.
REVEL	Benign	0.051
Sift	Benign	0.37	.;.;T;.;.
Sift4G	Benign	0.47	T;T;T;T;T
Polyphen		0.19	.;.;B;B;.
Vest4		0.16
MutPred		0.24		.;.;Gain of phosphorylation at P131 (P = 0.0311);.;.;
MVP		0.12
MPC		0.18
ClinPred		0.27	T
GERP RS		3.1
Varity_R		0.073
gMVP		0.42
Mutation Taster		=85/15	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: rs777309899; hg19: chr16-4659777;