16-28320448-C-T

Variant names:

• chr16-28320448-C-T
• NM_001024401.3:c.802C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001024401.3(SBK1):​c.802C>T​(p.Arg268Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SBK1 NM_001024401.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83
• Publications: 0 publications found

Genes affected

SBK1 (HGNC:17699): (SH3 domain binding kinase 1) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in peptidyl-serine phosphorylation and peptidyl-threonine phosphorylation. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024401.3. 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
	SBK1	NM_001024401.3	MANE Select	c.802C>T	p.Arg268Cys	missense	Exon 4 of 4	NP_001019572.1	Q52WX2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBK1	ENST00000341901.5	TSL:1 MANE Select	c.802C>T	p.Arg268Cys	missense	Exon 4 of 4	ENSP00000343248.4	Q52WX2
	SBK1	ENST00000671413.3		c.1066C>T	p.Arg356Cys	missense	Exon 4 of 4	ENSP00000499661.3	A0A590UK17

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1428148 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 710920

African (AFR) AF: 0.00 AC: 0 AN: 32342

American (AMR) AF: 0.00 AC: 0 AN: 41904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25252

East Asian (EAS) AF: 0.00 AC: 0 AN: 38508

South Asian (SAS) AF: 0.00 AC: 0 AN: 85200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102294

Other (OTH) AF: 0.00 AC: 0 AN: 59024

GnomAD4 genome Cov.: 31

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	0.27
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.85	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.8
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.46
Sift	Benign	0.051	T
Sift4G	Uncertain	0.052	T
Polyphen		1.0	D
Vest4		0.54
MutPred		0.59		Loss of MoRF binding (P = 0.0076)
MVP		0.91
ClinPred		0.98	D
GERP RS		3.0
Varity_R		0.33
gMVP		0.93

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

hg19: chr16-28331769;