16-4609775-G-A

Variant names:

• chr16-4609775-G-A
• rs369340092
• NM_145253.3:c.392C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145253.3(UBALD1):​c.392C>T​(p.Pro131Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,506,106 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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. P131A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (1 hom.)
• Consequence: UBALD1 NM_145253.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11706138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBALD1	NM_145253.3	c.392C>T	p.Pro131Leu	missense_variant	Exon 3 of 3	ENST00000283474.12	NP_660296.1
UBALD1	NM_001330467.2	c.317C>T	p.Pro106Leu	missense_variant	Exon 3 of 3		NP_001317396.1
UBALD1	NM_001411032.1	c.*208C>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.392C>T	p.Pro131Leu	missense_variant	Exon 3 of 3	1	NM_145253.3	ENSP00000283474.6

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 151996 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000156 AC: 23 AN: 147900 AF XY: 0.000137

Gnomad AFR exome AF: 0.000173

Gnomad AMR exome AF: 0.0000523

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000214

Gnomad NFE exome AF: 0.000244

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000352 AC: 476 AN: 1354110 Hom.: 1 Cov.: 32 AF XY: 0.000363 AC XY: 241 AN XY: 663626

African (AFR) AF: 0.000102 AC: 3 AN: 29532

American (AMR) AF: 0.0000714 AC: 2 AN: 28004

Ashkenazi Jewish (ASJ) AF: 0.0000512 AC: 1 AN: 19546

East Asian (EAS) AF: 0.0000798 AC: 3 AN: 37588

South Asian (SAS) AF: 0.0000143 AC: 1 AN: 70008

European-Finnish (FIN) AF: 0.0000653 AC: 3 AN: 45938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4978

European-Non Finnish (NFE) AF: 0.000425 AC: 452 AN: 1063032

Other (OTH) AF: 0.000198 AC: 11 AN: 55484

GnomAD4 genome AF: 0.000138 AC: 21 AN: 151996 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74236

African (AFR) AF: 0.0000242 AC: 1 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 67922

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000212

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000368 AC: 3

ExAC AF: 0.000175 AC: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.392C>T (p.P131L) 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 392, causing the proline (P) at amino acid position 131 to be replaced by a leucine (L). 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	0.081
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0069	.;.;T;T;.
Eigen	Benign	-0.061
Eigen_PC	Benign	-0.021
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.78	T;T;T;T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	.;.;L;.;.
PhyloP100		3.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.1	.;.;N;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.018	.;.;D;.;.
Sift4G	Uncertain	0.011	D;D;D;D;D
Polyphen		0.56	.;.;P;P;.
Vest4		0.38
MVP		0.17
MPC		0.16
ClinPred		0.052	T
GERP RS		3.9
Varity_R		0.083
gMVP		0.40
Mutation Taster		=89/11	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: rs369340092; hg19: chr16-4659776;