18-44951648-G-T

Variant names:

• chr18-44951648-G-T
• rs199810775
• NM_015559.3:c.2308G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015559.3(SETBP1):​c.2308G>T​(p.Ala770Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SETBP1 NM_015559.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.32

Genes affected

SETBP1 (HGNC:15573): (SET binding protein 1) This gene encodes a protein which contains a several motifs including a ski homology region and a SET-binding region in addition to three nuclear localization signals. The encoded protein has been shown to bind the SET nuclear oncogene which is involved in DNA replication. Mutations in this gene are associated with Schinzel-Giedion midface retraction syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETBP1	NM_015559.3	c.2308G>T	p.Ala770Ser	missense_variant	Exon 4 of 6	ENST00000649279.2	NP_056374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETBP1	ENST00000649279.2	c.2308G>T	p.Ala770Ser	missense_variant	Exon 4 of 6		NM_015559.3	ENSP00000497406.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Benign	0.46	N;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.12	.;N
REVEL	Uncertain	0.36
Sift	Benign	0.11	.;T
Sift4G	Benign	0.44	.;T
Polyphen		1.0	D;D
Vest4		0.47
MutPred		0.14		Gain of glycosylation at A770 (P = 0.0287);Gain of glycosylation at A770 (P = 0.0287);
MVP		0.54
MPC		0.87
ClinPred		0.87	D
GERP RS		6.2
Varity_R		0.12
gMVP		0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs199810775; hg19: chr18-42531613;