17-76270422-C-G

Variant names:

• chr17-76270422-C-G
• rs1273706945
• NM_182565.4:c.412C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182565.4(UBALD2):​c.412C>G​(p.Arg138Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,377,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. R138C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: UBALD2 NM_182565.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 0 publications found

Genes affected

UBALD2 (HGNC:28438): (UBA like domain containing 2)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04418063).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182565.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBALD2	NM_182565.4	MANE Select	c.412C>G	p.Arg138Gly	missense	Exon 3 of 3	NP_872371.1	Q8IYN6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBALD2	ENST00000327490.8	TSL:1 MANE Select	c.412C>G	p.Arg138Gly	missense	Exon 3 of 3	ENSP00000331298.6	Q8IYN6
	UBALD2	ENST00000864754.1		c.349C>G	p.Arg117Gly	missense	Exon 2 of 2	ENSP00000534813.1
	UBALD2	ENST00000589240.1	TSL:2	c.232C>G	p.Arg78Gly	missense	Exon 2 of 2	ENSP00000466518.1	K7EMI7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1377298 Hom.: 0 Cov.: 43 AF XY: 0.00000295 AC XY: 2 AN XY: 678424

African (AFR) AF: 0.00 AC: 0 AN: 31096

American (AMR) AF: 0.00 AC: 0 AN: 34124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24562

East Asian (EAS) AF: 0.00 AC: 0 AN: 35558

South Asian (SAS) AF: 0.00 AC: 0 AN: 78266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4036

European-Non Finnish (NFE) AF: 0.00000373 AC: 4 AN: 1072540

Other (OTH) AF: 0.00 AC: 0 AN: 57240

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.93
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.6
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.083
Sift	Benign	0.31	T
Sift4G	Benign	0.34	T
Polyphen		0.012	B
Vest4		0.091
MutPred		0.11		Gain of catalytic residue at Q140 (P = 0.1296)
MVP		0.088
MPC		1.7
ClinPred		0.15	T
GERP RS		-2.6
Varity_R		0.064
gMVP		0.18
Mutation Taster		=88/12	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: rs1273706945; hg19: chr17-74266503;