chr16-4609787-G-C

Variant names:

• chr16-4609787-G-C
• rs773973529
• NM_145253.3:c.380C>G

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.380C>G​(p.Ala127Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,355,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A127V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: UBALD1 NM_145253.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• 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=0.06892291).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBALD1	NM_145253.3	c.380C>G	p.Ala127Gly	missense_variant	Exon 3 of 3	ENST00000283474.12	NP_660296.1
UBALD1	NM_001330467.2	c.305C>G	p.Ala102Gly	missense_variant	Exon 3 of 3		NP_001317396.1
UBALD1	NM_001411032.1	c.*196C>G		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.380C>G	p.Ala127Gly	missense_variant	Exon 3 of 3	1	NM_145253.3	ENSP00000283474.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1355662 Hom.: 0 Cov.: 32 AF XY: 0.00000150 AC XY: 1 AN XY: 664472

⚠️ 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: 29640

American (AMR) AF: 0.00 AC: 0 AN: 28244

Ashkenazi Jewish (ASJ) AF: 0.0000510 AC: 1 AN: 19606

East Asian (EAS) AF: 0.00 AC: 0 AN: 37586

South Asian (SAS) AF: 0.00 AC: 0 AN: 70512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5064

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063274

Other (OTH) AF: 0.0000180 AC: 1 AN: 55614

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.60
DEOGEN2	Benign	0.0023	.;.;T;T;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.67	T;T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.069	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;.;L;.;.
PhyloP100		1.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.1	.;.;N;.;.
REVEL	Benign	0.029
Sift	Benign	0.20	.;.;T;.;.
Sift4G	Benign	0.29	T;T;T;T;T
Polyphen		0.0	.;.;B;B;.
Vest4		0.12
MutPred		0.15		.;.;Gain of relative solvent accessibility (P = 0.0023);.;.;
MVP		0.14
MPC		0.16
ClinPred		0.029	T
GERP RS		2.8
Varity_R		0.048
gMVP		0.28
Mutation Taster		=95/5	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: rs773973529; hg19: chr16-4659788;