16-4609936-G-C

Variant names:

• chr16-4609936-G-C
• rs144958752
• NM_145253.3:c.231C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145253.3(UBALD1):​c.231C>G​(p.Asp77Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,447,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: UBALD1 NM_145253.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.150

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42132568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBALD1	NM_145253.3	c.231C>G	p.Asp77Glu	missense_variant	Exon 3 of 3	ENST00000283474.12	NP_660296.1
UBALD1	NM_001411032.1	c.*47C>G		3_prime_UTR_variant	Exon 3 of 3		NP_001397961.1
UBALD1	NM_001330467.2	c.184-28C>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.231C>G	p.Asp77Glu	missense_variant	Exon 3 of 3	1	NM_145253.3	ENSP00000283474.6

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000881 AC: 2 AN: 227032 AF XY: 0.0000161

Gnomad AFR exome AF: 0.00

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: 0.0000201

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000484 AC: 7 AN: 1447342 Hom.: 0 Cov.: 32 AF XY: 0.00000418 AC XY: 3 AN XY: 718508

African (AFR) AF: 0.00 AC: 0 AN: 33222

American (AMR) AF: 0.00 AC: 0 AN: 43116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25454

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.00 AC: 0 AN: 84710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00000453 AC: 5 AN: 1104450

Other (OTH) AF: 0.0000335 AC: 2 AN: 59718

GnomAD4 genome Cov.: 29

ExAC AF: 0.00000829 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.231C>G (p.D77E) 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 231, causing the aspartic acid (D) at amino acid position 77 to be replaced by a glutamic acid (E). 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	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	.;.;T;T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.91	D;D;T;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.42	T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.8	.;.;L;.;.
PhyloP100		-0.15
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.9	.;.;D;.;.
REVEL	Uncertain	0.34
Sift	Benign	0.15	.;.;T;.;.
Sift4G	Benign	0.16	T;T;T;T;T
Polyphen		0.90, 1.0	.;.;P;D;.
Vest4		0.88
MutPred		0.31		.;.;Gain of glycosylation at P73 (P = 0.1534);.;.;
MVP		0.70
MPC		0.33
ClinPred		0.84	D
GERP RS		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144958752; hg19: chr16-4659937;