chr21-43093182-C-T

Variant names:

• chr21-43093182-C-T
• rs1450304522
• NM_006758.3:c.643G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP2 BP4

The NM_006758.3(U2AF1):​c.643G>A​(p.Gly215Ser) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: U2AF1 NM_006758.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.43
• Publications: 0 publications found

Genes affected

U2AF1 (HGNC:12453): (U2 small nuclear RNA auxiliary factor 1) This gene belongs to the splicing factor SR family of genes. U2 auxiliary factor, comprising a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the small subunit which plays a critical role in both constitutive and enhancer-dependent RNA splicing by directly mediating interactions between the large subunit and proteins bound to the enhancers. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ENSG00000295227 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 3.8478 (above the threshold of 3.09). Trascript score misZ: NaN (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.32032034).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006758.3. 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
	U2AF1	NM_006758.3	MANE Select	c.643G>A	p.Gly215Ser	missense	Exon 8 of 8	NP_006749.1	Q01081-1
	U2AF1	NM_001025203.1		c.643G>A	p.Gly215Ser	missense	Exon 8 of 8	NP_001020374.1	Q01081-2
	U2AF1	NM_001025204.2		c.424G>A	p.Gly142Ser	missense	Exon 9 of 9	NP_001020375.1	Q01081-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	U2AF1	ENST00000291552.9	TSL:1 MANE Select	c.643G>A	p.Gly215Ser	missense	Exon 8 of 8	ENSP00000291552.4	Q01081-1
	U2AF1	ENST00000380276.6	TSL:1	c.643G>A	p.Gly215Ser	missense	Exon 8 of 8	ENSP00000369629.2	Q01081-2
	U2AF1	ENST00000459639.5	TSL:1	c.424G>A	p.Gly142Ser	missense	Exon 7 of 7	ENSP00000418705.1	Q01081-4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249506 AF XY: 0.00

Gnomad AFR exome AF: 0.0000634

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.0000468 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Benign	0.73
Eigen	Benign	0.10
Eigen_PC	Benign	0.041
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.60	D
MutationAssessor	Benign	0.90	L
PhyloP100		4.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.20	N
REVEL	Uncertain	0.38
Sift	Benign	0.64	T
Sift4G	Benign	0.37	T
Polyphen		1.0	D
Vest4		0.39
MutPred		0.35		Gain of phosphorylation at G215 (P = 2e-04)
MVP		0.81
MPC		1.5
ClinPred		0.18	T
GERP RS		4.8
Varity_R		0.13
gMVP		0.50
Mutation Taster		=36/64	disease causing

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: rs1450304522; hg19: chr21-44513292; COSMIC: COSV99373514;