16-28317471-C-T

Variant names:

• chr16-28317471-C-T
• NM_001024401.3:c.80C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001024401.3(SBK1):​c.80C>T​(p.Ala27Val) 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 benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SBK1 NM_001024401.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.896

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18017024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBK1	NM_001024401.3	c.80C>T	p.Ala27Val	missense_variant	Exon 2 of 4	ENST00000341901.5	NP_001019572.1
SBK1	XM_005255315.5	c.182C>T	p.Ala61Val	missense_variant	Exon 2 of 4		XP_005255372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBK1	ENST00000341901.5	c.80C>T	p.Ala27Val	missense_variant	Exon 2 of 4	1	NM_001024401.3	ENSP00000343248.4
SBK1	ENST00000671413.3	c.344C>T	p.Ala115Val	missense_variant	Exon 2 of 4			ENSP00000499661.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.80C>T (p.A27V) alteration is located in exon 2 (coding exon 1) of the SBK1 gene. This alteration results from a C to T substitution at nucleotide position 80, causing the alanine (A) at amino acid position 27 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.15
Sift	Benign	0.044	D
Sift4G	Benign	0.16	T
Polyphen		0.95	P
Vest4		0.19
MutPred		0.20		Loss of glycosylation at P25 (P = 0.1287);
MVP		0.65
ClinPred		0.19	T
GERP RS		3.4
Varity_R		0.037
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-28328792;