chr16-4609808-G-T

Variant names:

• chr16-4609808-G-T
• rs371867321
• NM_145253.3:c.359C>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.359C>A​(p.Ala120Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000731 in 1,368,648 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. A120V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: UBALD1 NM_145253.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23
• 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=0.11487371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBALD1	NM_145253.3	c.359C>A	p.Ala120Glu	missense_variant	Exon 3 of 3	ENST00000283474.12	NP_660296.1
UBALD1	NM_001330467.2	c.284C>A	p.Ala95Glu	missense_variant	Exon 3 of 3		NP_001317396.1
UBALD1	NM_001411032.1	c.*175C>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.359C>A	p.Ala120Glu	missense_variant	Exon 3 of 3	1	NM_145253.3	ENSP00000283474.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.31e-7 AC: 1 AN: 1368648 Hom.: 0 Cov.: 32 AF XY: 0.00000149 AC XY: 1 AN XY: 672146

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30366

American (AMR) AF: 0.00 AC: 0 AN: 30808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20288

East Asian (EAS) AF: 0.00 AC: 0 AN: 38084

South Asian (SAS) AF: 0.00 AC: 0 AN: 72566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5260

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068126

Other (OTH) AF: 0.0000178 AC: 1 AN: 56248

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.69
DEOGEN2	Benign	0.00073	.;.;T;T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.65	T;T;T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;.;N;.;.
PhyloP100		4.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.17	.;.;N;.;.
REVEL	Benign	0.060
Sift	Benign	0.28	.;.;T;.;.
Sift4G	Benign	0.28	T;T;T;T;T
Polyphen		0.76, 0.17	.;.;P;B;.
Vest4		0.27
MutPred		0.24		.;.;Gain of solvent accessibility (P = 0.0145);.;.;
MVP		0.22
MPC		0.19
ClinPred		0.13	T
GERP RS		2.8
Varity_R		0.058
gMVP		0.25

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: rs371867321; hg19: chr16-4659809;