chr16-4609862-G-A

Variant names:

• chr16-4609862-G-A
• rs531541598
• NM_145253.3:c.305C>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.305C>T​(p.Ala102Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000042 in 1,523,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A102E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: UBALD1 NM_145253.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.99

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=0.12081057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBALD1	NM_145253.3	c.305C>T	p.Ala102Val	missense_variant	Exon 3 of 3	ENST00000283474.12	NP_660296.1
UBALD1	NM_001330467.2	c.230C>T	p.Ala77Val	missense_variant	Exon 3 of 3		NP_001317396.1
UBALD1	NM_001411032.1	c.*121C>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.305C>T	p.Ala102Val	missense_variant	Exon 3 of 3	1	NM_145253.3	ENSP00000283474.6

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 151930 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000283 AC: 4 AN: 141410 AF XY: 0.0000262

Gnomad AFR exome AF: 0.000101

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000510

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000394 AC: 54 AN: 1371446 Hom.: 0 Cov.: 32 AF XY: 0.0000372 AC XY: 25 AN XY: 672708

African (AFR) AF: 0.0000318 AC: 1 AN: 31436

American (AMR) AF: 0.0000623 AC: 2 AN: 32080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21316

East Asian (EAS) AF: 0.0000530 AC: 2 AN: 37724

South Asian (SAS) AF: 0.000109 AC: 8 AN: 73460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5420

European-Non Finnish (NFE) AF: 0.0000356 AC: 38 AN: 1066744

Other (OTH) AF: 0.0000530 AC: 3 AN: 56626

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 152048 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74332

African (AFR) AF: 0.0000723 AC: 3 AN: 41480

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67930

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.0000540 Hom.: 0

ExAC AF: 0.0000513 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.305C>T (p.A102V) alteration is located in exon 3 (coding exon 3) of the UBALD1 gene. This alteration results from a C to T substitution at nucleotide position 305, causing the alanine (A) at amino acid position 102 to be replaced by a valine (V). 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	0.098
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0045	.;.;T;T;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;D;D;D;T;D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;.;L;.;.;.
PhyloP100		9.0
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.1	.;.;N;.;.;.
REVEL	Benign	0.13
Sift	Benign	0.17	.;.;T;.;.;.
Sift4G	Uncertain	0.053	T;T;T;T;D;T
Polyphen		0.20	.;.;B;B;.;.
Vest4		0.19
MutPred		0.23		.;.;Gain of sheet (P = 0.0221);.;.;.;
MVP		0.17
MPC		0.16
ClinPred		0.12	T
GERP RS		4.1
Varity_R		0.060
gMVP		0.32
Mutation Taster		=84/16	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

Publications

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Other links and lift over

dbSNP: rs531541598; hg19: chr16-4659863;