19-4262039-C-T

Variant names:

• chr19-4262039-C-T
• rs8106603
• NM_018074.6:c.633C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018074.6(YJU2):​c.633C>T​(p.Ser211Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00565 in 1,613,122 control chromosomes in the GnomAD database, including 449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (222 hom., cov: 31)
  • Exomes 𝑓: 0.0032 (227 hom.)
• Consequence: YJU2 NM_018074.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -7.21
• Publications: 1 publications found

Genes affected

YJU2 (HGNC:25518): (YJU2 splicing factor homolog) Predicted to enable metal ion binding activity. Predicted to be involved in RNA splicing and negative regulation of DNA damage response, signal transduction by p53 class mediator. Part of U2-type catalytic step 1 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 19-4262039-C-T is Benign according to our data. Variant chr19-4262039-C-T is described in ClinVar as Benign. ClinVar VariationId is 785913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0991 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018074.6. 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
	YJU2	NM_018074.6	MANE Select	c.633C>T	p.Ser211Ser	synonymous	Exon 6 of 8	NP_060544.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YJU2	ENST00000262962.12	TSL:1 MANE Select	c.633C>T	p.Ser211Ser	synonymous	Exon 6 of 8	ENSP00000262962.6	Q9BW85
	YJU2	ENST00000872338.1		c.633C>T	p.Ser211Ser	synonymous	Exon 6 of 8	ENSP00000542397.1

Frequencies

GnomAD3 genomes AF: 0.0292 AC: 4437 AN: 152028 Hom.: 219 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00768 AC: 1921 AN: 250234 AF XY: 0.00571

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.00515

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00318 AC: 4644 AN: 1460976 Hom.: 227 Cov.: 31 AF XY: 0.00276 AC XY: 2006 AN XY: 726832

African (AFR) AF: 0.108 AC: 3628 AN: 33460

American (AMR) AF: 0.00573 AC: 256 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52672

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5768

European-Non Finnish (NFE) AF: 0.000268 AC: 298 AN: 1111910

Other (OTH) AF: 0.00674 AC: 407 AN: 60376

GnomAD4 genome AF: 0.0293 AC: 4465 AN: 152146 Hom.: 222 Cov.: 31 AF XY: 0.0284 AC XY: 2115 AN XY: 74384

African (AFR) AF: 0.102 AC: 4218 AN: 41506

American (AMR) AF: 0.0117 AC: 178 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 67986

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.0121 Hom.: 34

Bravo AF: 0.0338

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.016
DANN	Benign	0.79
PhyloP100		-7.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs8106603; hg19: chr19-4262036;