chr17-76270422-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_182565.4(UBALD2):​c.412C>T​(p.Arg138Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,529,428 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: UBALD2 NM_182565.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039872795).
• BP6: Variant 17-76270422-C-T is Benign according to our data. Variant chr17-76270422-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2339377.Status of the report is criteria_provided_single_submitter, 1 stars.

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>T	p.Arg138Cys	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>T	p.Arg138Cys	missense	Exon 3 of 3	ENSP00000331298.6	Q8IYN6
	UBALD2	ENST00000864754.1		c.349C>T	p.Arg117Cys	missense	Exon 2 of 2	ENSP00000534813.1
	UBALD2	ENST00000589240.1	TSL:2	c.232C>T	p.Arg78Cys	missense	Exon 2 of 2	ENSP00000466518.1	K7EMI7

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152130 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000393 AC: 5 AN: 127172 AF XY: 0.0000431

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: 0.0000655

Gnomad OTH exome AF: 0.000260

GnomAD4 exome AF: 0.0000160 AC: 22 AN: 1377298 Hom.: 0 Cov.: 43 AF XY: 0.0000177 AC XY: 12 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: 0.0000128 AC: 1 AN: 78266

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

Middle Eastern (MID) AF: 0.000496 AC: 2 AN: 4036

European-Non Finnish (NFE) AF: 0.0000159 AC: 17 AN: 1072540

Other (OTH) AF: 0.0000349 AC: 2 AN: 57240

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152130 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74302

African (AFR) AF: 0.0000724 AC: 3 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000321 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N
PhyloP100		2.6
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.071
Sift	Benign	0.19	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.062
MutPred		0.15		Loss of solvent accessibility (P = 0.1077)
MVP		0.067
MPC		1.6
ClinPred		0.051	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.052
gMVP		0.24
Mutation Taster		=90/10	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;