NM_001370096.2:c.688G>C

Variant names:

• chr19-55530092-C-G
• rs1438223677
• NM_001370096.2:c.688G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370096.2(SBK2):​c.688G>C​(p.Ala230Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000775 in 1,290,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A230T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: SBK2 NM_001370096.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• Publications: 2 publications found

Genes affected

SBK2 (HGNC:34416): (SH3 domain binding kinase family member 2) Predicted to enable MAP kinase kinase activity. Predicted to be involved in MAPK cascade and protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28477407).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370096.2. 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
	SBK2	NM_001370096.2	MANE Select	c.688G>C	p.Ala230Pro	missense	Exon 4 of 4	NP_001357025.1	P0C263

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBK2	ENST00000413299.6	TSL:5 MANE Select	c.688G>C	p.Ala230Pro	missense	Exon 4 of 4	ENSP00000389015.2	P0C263
	SBK2	ENST00000344158.4	TSL:2	c.688G>C	p.Ala230Pro	missense	Exon 3 of 3	ENSP00000345044.3	P0C263
	SBK2	ENST00000912390.1		c.688G>C	p.Ala230Pro	missense	Exon 4 of 4	ENSP00000582449.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000205 AC: 1 AN: 48812 AF XY: 0.0000376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000193

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.75e-7 AC: 1 AN: 1290412 Hom.: 0 Cov.: 34 AF XY: 0.00000159 AC XY: 1 AN XY: 629096

African (AFR) AF: 0.00 AC: 0 AN: 25652

American (AMR) AF: 0.00 AC: 0 AN: 20964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19118

East Asian (EAS) AF: 0.0000312 AC: 1 AN: 32084

South Asian (SAS) AF: 0.00 AC: 0 AN: 64912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4580

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1035726

Other (OTH) AF: 0.00 AC: 0 AN: 53468

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.17
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.13
Sift	Benign	0.26	T
Sift4G	Benign	0.29	T
Polyphen		0.94	P
Vest4		0.51
MutPred		0.48		Gain of glycosylation at A230 (P = 0.007)
MVP		0.59
MPC		2.1
ClinPred		0.21	T
GERP RS		0.60
Varity_R		0.071
gMVP		0.72
Mutation Taster		=96/4	polymorphism

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: rs1438223677; hg19: chr19-56041459;