rs200575140

Variant names:

• chr19-55529804-C-A
• rs200575140
• NM_001370096.2:c.976G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-55529804-C-A
• chr19-55529804-C-G
• chr19-55529804-C-T

Variant summary

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

The NM_001370096.2(SBK2):​c.976G>T​(p.Gly326Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G326R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SBK2 NM_001370096.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.788

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.976G>T	p.Gly326Trp	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.976G>T	p.Gly326Trp	missense	Exon 4 of 4	ENSP00000389015.2	P0C263
	SBK2	ENST00000344158.4	TSL:2	c.976G>T	p.Gly326Trp	missense	Exon 3 of 3	ENSP00000345044.3	P0C263
	SBK2	ENST00000912390.1		c.976G>T	p.Gly326Trp	missense	Exon 4 of 4	ENSP00000582449.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452222 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 722870

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111654

Other (OTH) AF: 0.0000166 AC: 1 AN: 60284

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.088	T
Eigen	Benign	0.080
Eigen_PC	Benign	-0.057
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.42
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.47		Loss of helix (P = 0.0068)
MVP		0.76
MPC		2.3
ClinPred		0.96	D
GERP RS		3.9
Varity_R		0.25
gMVP		0.63
Mutation Taster		=92/8	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: rs200575140; hg19: chr19-56041171;