chr4-5051876-C-A

Variant names:

• chr4-5051876-C-A
• rs1741799154
• NM_018401.3:c.13C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018401.3(STK32B):​c.13C>A​(p.His5Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STK32B NM_018401.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.26

Genes affected

STK32B (HGNC:14217): (serine/threonine kinase 32B) This gene encodes a serine-threonine protein kinase. Serine-threonine kinases transfer phosphate molecules to the oxygen atoms of serine and threonine. A genomic deletion affecting this gene has been associated with Ellis-van Creveld syndrome, an autosomal recessive skeletal dysplasia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17586622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK32B	NM_018401.3	c.13C>A	p.His5Asn	missense_variant	Exon 1 of 12	ENST00000282908.10	NP_060871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK32B	ENST00000282908.10	c.13C>A	p.His5Asn	missense_variant	Exon 1 of 12	1	NM_018401.3	ENSP00000282908.5
STK32B	ENST00000512018.5	n.13C>A		non_coding_transcript_exon_variant	Exon 1 of 13	1		ENSP00000422820.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447614 Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 2 AN XY: 718952

African (AFR) AF: 0.00 AC: 0 AN: 32868

American (AMR) AF: 0.00 AC: 0 AN: 43382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25846

East Asian (EAS) AF: 0.00 AC: 0 AN: 38514

South Asian (SAS) AF: 0.00 AC: 0 AN: 83544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105770

Other (OTH) AF: 0.00 AC: 0 AN: 59722

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.13C>A (p.H5N) alteration is located in exon 1 (coding exon 1) of the STK32B gene. This alteration results from a C to A substitution at nucleotide position 13, causing the histidine (H) at amino acid position 5 to be replaced by an asparagine (N). 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	0.058
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.18	N
PhyloP100		2.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.10
Sift	Benign	0.43	T
Sift4G	Benign	0.52	T
Polyphen		0.0050	B
Vest4		0.52
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0249);
MVP		0.76
MPC		0.060
ClinPred		0.83	D
GERP RS		4.6
PromoterAI		0.034	Neutral
Varity_R		0.14
gMVP		0.090
Mutation Taster		=89/11	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

Publications

LitVar

Other links and lift over

dbSNP: rs1741799154; hg19: chr4-5053603;