chr2-228018254-T-G

Position:

• chr2-228018254-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142644.2(SPHKAP):​c.2600A>C​(p.Gln867Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. Q867R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPHKAP NM_001142644.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743

Genes affected

SPHKAP (HGNC:30619): (SPHK1 interactor, AKAP domain containing) Enables protein kinase A binding activity. Predicted to be located in Z disc. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

LOC105373918 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07585129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPHKAP	NM_001142644.2	c.2600A>C	p.Gln867Pro	missense_variant	7/12	ENST00000392056.8	NP_001136116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPHKAP	ENST00000392056.8	c.2600A>C	p.Gln867Pro	missense_variant	7/12	1	NM_001142644.2	ENSP00000375909.3
SPHKAP	ENST00000344657.5	c.2600A>C	p.Gln867Pro	missense_variant	7/11	1		ENSP00000339886.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.1
DANN	Benign	0.90
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.98	N;N
REVEL	Benign	0.046
Sift	Uncertain	0.021	D;D
Sift4G	Benign	0.25	T;T
Polyphen		0.29	B;P
Vest4		0.17
MutPred		0.14		Gain of glycosylation at Q867 (P = 0.0234);Gain of glycosylation at Q867 (P = 0.0234);
MVP		0.092
MPC		0.071
ClinPred		0.11	T
GERP RS		-0.75
Varity_R		0.17
gMVP		0.26

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: rs3828161; hg19: chr2-228882970;