SPHKAP p.His847Gln

Variant names:

• chr2-228018313-A-T
• NM_001142644.2:c.2541T>A
• SPHKAP p.His847Gln

Your query was ambiguous. Multiple possible variants found:

• chr2-228018313-A-T
• chr2-228018313-A-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142644.2(SPHKAP):​c.2541T>A​(p.His847Gln) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPHKAP NM_001142644.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050015062).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142644.2. 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
	SPHKAP	NM_001142644.2	MANE Select	c.2541T>A	p.His847Gln	missense	Exon 7 of 12	NP_001136116.1	Q2M3C7-1
	SPHKAP	NM_030623.4		c.2541T>A	p.His847Gln	missense	Exon 7 of 11	NP_085126.2	Q2M3C7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPHKAP	ENST00000392056.8	TSL:1 MANE Select	c.2541T>A	p.His847Gln	missense	Exon 7 of 12	ENSP00000375909.3	Q2M3C7-1
	SPHKAP	ENST00000344657.5	TSL:1	c.2541T>A	p.His847Gln	missense	Exon 7 of 11	ENSP00000339886.5	Q2M3C7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.66
DANN	Benign	0.76
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.23
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.10
Sift	Benign	0.13	T
Sift4G	Benign	0.48	T
Varity_R		0.052
gMVP		0.14
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-228883029;