chr2-227991150-G-C

Variant names:

• chr2-227991150-G-C
• rs16824283
• NM_001142644.2:c.4809C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142644.2(SPHKAP):​c.4809C>G​(p.Ser1603Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,613,886 control chromosomes in the GnomAD database, including 53,582 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.20 (3705 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49877 hom.)
• Consequence: SPHKAP NM_001142644.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0060194135).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPHKAP	NM_001142644.2	c.4809C>G	p.Ser1603Arg	missense_variant	Exon 11 of 12	ENST00000392056.8	NP_001136116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPHKAP	ENST00000392056.8	c.4809C>G	p.Ser1603Arg	missense_variant	Exon 11 of 12	1	NM_001142644.2	ENSP00000375909.3
SPHKAP	ENST00000344657.5	c.4722C>G	p.Ser1574Arg	missense_variant	Exon 10 of 11	1		ENSP00000339886.5
SPHKAP	ENST00000490603.1	n.302C>G		non_coding_transcript_exon_variant	Exon 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30491 AN: 152002 Hom.: 3711 Cov.: 32

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.214

GnomAD3 exomes AF: 0.225 AC: 56379 AN: 250726 Hom.: 7000 AF XY: 0.229 AC XY: 30990 AN XY: 135492

Gnomad AFR exome AF: 0.0578

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.233

Gnomad SAS exome AF: 0.176

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.271

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.256 AC: 374860 AN: 1461766 Hom.: 49877 Cov.: 36 AF XY: 0.255 AC XY: 185717 AN XY: 727180

Gnomad4 AFR exome AF: 0.0558

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.200 AC: 30478 AN: 152120 Hom.: 3705 Cov.: 32 AF XY: 0.201 AC XY: 14954 AN XY: 74358

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.210

Alfa AF: 0.256 Hom.: 3944

Bravo AF: 0.193

TwinsUK AF: 0.275 AC: 1018

ALSPAC AF: 0.274 AC: 1055

ESP6500AA AF: 0.0672 AC: 296

ESP6500EA AF: 0.270 AC: 2318

ExAC AF: 0.222 AC: 27003

Asia WGS AF: 0.169 AC: 588 AN: 3478

EpiCase AF: 0.273

EpiControl AF: 0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.72	T;T
MetaRNN	Benign	0.0060	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.026	D;D
Sift4G	Uncertain	0.031	D;D
Polyphen		0.97	D;P
Vest4		0.084
MutPred		0.067		Loss of glycosylation at S1603 (P = 0.0296);.;
MPC		0.28
ClinPred		0.046	T
GERP RS		-2.2
Varity_R		0.34
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16824283; hg19: chr2-228855866; COSMIC: COSV60872310;