Genetic Variant NM_001024401.3:c.964C>G (chr16-28320610-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001024401.3(SBK1):c.964C>G(p.Arg322Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,405,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SBK1
NM_001024401.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

Variant links:

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]

SBK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059756756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBK1	NM_001024401.3 link	c.964C>G	p.Arg322Gly	missense_variant	Exon 4 of 4	ENST00000341901.5	NP_001019572.1	Q52WX2
SBK1	XM_005255315.5 link	c.1066C>G	p.Arg356Gly	missense_variant	Exon 4 of 4		XP_005255372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBK1	ENST00000341901.5 link	c.964C>G	p.Arg322Gly	missense_variant	Exon 4 of 4	1	NM_001024401.3	ENSP00000343248.4		Q52WX2
SBK1	ENST00000671413.3 link	c.1228C>G	p.Arg410Gly	missense_variant	Exon 4 of 4			ENSP00000499661.3		A0A590UK17

Frequencies

GnomAD3 genomes

AF:

0.0000601

AC:

AN:

149772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000665

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000595

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.000107

AC:

AN:

46782

Hom.:

AF XY:

0.000144

AC XY:

AN XY:

27686

show subpopulations

Gnomad AFR exome

AF:

0.000785

Gnomad AMR exome

AF:

0.000588

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000119

AC:

AN:

1256178

Hom.:

Cov.:

AF XY:

0.0000163

AC XY:

AN XY:

614218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000413

Gnomad4 AMR exome

AF:

0.000331

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000690

Gnomad4 OTH exome

AF:

0.0000197

GnomAD4 genome

AF:

0.0000601

AC:

AN:

149772

Hom.:

Cov.:

AF XY:

0.0000547

AC XY:

AN XY:

73074

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.0000665

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000595

Gnomad4 OTH

AF:

0.00145

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000214

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.964C>G (p.R322G) alteration is located in exon 4 (coding exon 3) of the SBK1 gene. This alteration results from a C to G substitution at nucleotide position 964, causing the arginine (R) at amino acid position 322 to be replaced by a glycine (G). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Benign

-0.0042

Eigen_PC

Benign

0.038

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-0.41

REVEL

Benign

0.042

Sift

Uncertain

0.011

Sift4G

Benign

0.10

Polyphen

0.80

Vest4

0.25

MutPred

0.24

Loss of glycosylation at P325 (P = 0.0817);

MVP

0.42

ClinPred

0.055

GERP RS

3.3

Varity_R

0.11

gMVP

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over