NM_001142644.2:c.4910G>A

Variant names:

• chr2-227991049-C-T
• rs746889542
• NM_001142644.2:c.4910G>A

Variant summary

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

The NM_001142644.2(SPHKAP):​c.4910G>A​(p.Gly1637Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G1637V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPHKAP NM_001142644.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.28
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.4910G>A	p.Gly1637Glu	missense	Exon 11 of 12	NP_001136116.1	Q2M3C7-1
	SPHKAP	NM_030623.4		c.4823G>A	p.Gly1608Glu	missense	Exon 10 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.4910G>A	p.Gly1637Glu	missense	Exon 11 of 12	ENSP00000375909.3	Q2M3C7-1
	SPHKAP	ENST00000344657.5	TSL:1	c.4823G>A	p.Gly1608Glu	missense	Exon 10 of 11	ENSP00000339886.5	Q2M3C7-2
	SPHKAP	ENST00000490603.1	TSL:4	n.403G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	0.00075	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.26
Sift	Benign	0.33	T
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.37		Gain of glycosylation at T1640 (P = 0.0799)
MVP		0.37
MPC		0.36
ClinPred		0.97	D
GERP RS		6.2
Varity_R		0.29
gMVP		0.67
Mutation Taster		=17/83	disease causing

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: rs746889542; hg19: chr2-228855765; COSMIC: COSV60875234;