rs1438223677

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-55530092-C-G
• chr19-55530092-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBK2	NM_001370096.2	c.688G>C	p.Ala230Pro	missense_variant	Exon 4 of 4	ENST00000413299.6	NP_001357025.1
SBK2	XM_011527227.3	c.*247G>C		3_prime_UTR_variant	Exon 4 of 4		XP_011525529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBK2	ENST00000413299.6	c.688G>C	p.Ala230Pro	missense_variant	Exon 4 of 4	5	NM_001370096.2	ENSP00000389015.2
SBK2	ENST00000344158.4	c.688G>C	p.Ala230Pro	missense_variant	Exon 3 of 3	2		ENSP00000345044.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000205 AC: 1 AN: 48812 Hom.: 0 AF XY: 0.0000376 AC XY: 1 AN XY: 26562

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000312

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.47	N;N
REVEL	Benign	0.13
Sift	Benign	0.26	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.94	P;P
Vest4		0.51
MutPred		0.48		Gain of glycosylation at A230 (P = 0.007);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

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: rs1438223677; hg19: chr19-56041459;