16-4609919-G-C

Variant names:

• chr16-4609919-G-C
• NM_145253.3:c.248C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_145253.3(UBALD1):​c.248C>G​(p.Ser83Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: UBALD1 NM_145253.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.93

Genes affected

UBALD1 (HGNC:29576): (UBA like domain containing 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBALD1	NM_145253.3	c.248C>G	p.Ser83Cys	missense_variant	Exon 3 of 3	ENST00000283474.12	NP_660296.1
UBALD1	NM_001411032.1	c.*64C>G		3_prime_UTR_variant	Exon 3 of 3		NP_001397961.1
UBALD1	NM_001330467.2	c.184-11C>G		intron_variant	Intron 2 of 2		NP_001317396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBALD1	ENST00000283474.12	c.248C>G	p.Ser83Cys	missense_variant	Exon 3 of 3	1	NM_145253.3	ENSP00000283474.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.248C>G (p.S83C) alteration is located in exon 3 (coding exon 3) of the UBALD1 gene. This alteration results from a C to G substitution at nucleotide position 248, causing the serine (S) at amino acid position 83 to be replaced by a cysteine (C). 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	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	.;.;T;T;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.78	D;D;D;D;D
MetaSVM	Uncertain	-0.072	T
MutationAssessor	Uncertain	2.2	.;.;M;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-4.2	.;.;D;.;.
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	.;.;D;.;.
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		1.0	.;.;D;D;.
Vest4		0.64
MutPred		0.34		.;.;Gain of catalytic residue at M81 (P = 0.0015);.;.;
MVP		0.47
MPC		0.67
ClinPred		0.99	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-4659920;