2-228018254-T-C

Variant names:

• chr2-228018254-T-C
• rs3828161
• NM_001142644.2:c.2600A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142644.2(SPHKAP):​c.2600A>G​(p.Gln867Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,986 control chromosomes in the GnomAD database, including 26,248 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.21 (3651 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22597 hom.)
• Consequence: SPHKAP NM_001142644.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743
• Publications: 20 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.5624375E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

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.2600A>G	p.Gln867Arg	missense	Exon 7 of 12	NP_001136116.1	Q2M3C7-1
	SPHKAP	NM_030623.4		c.2600A>G	p.Gln867Arg	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.2600A>G	p.Gln867Arg	missense	Exon 7 of 12	ENSP00000375909.3	Q2M3C7-1
	SPHKAP	ENST00000344657.5	TSL:1	c.2600A>G	p.Gln867Arg	missense	Exon 7 of 11	ENSP00000339886.5	Q2M3C7-2

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31425 AN: 152012 Hom.: 3641 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.194 AC: 48748 AN: 251372 AF XY: 0.184

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.410

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.168 AC: 245818 AN: 1461856 Hom.: 22597 Cov.: 36 AF XY: 0.165 AC XY: 120339 AN XY: 727230

African (AFR) AF: 0.284 AC: 9514 AN: 33480

American (AMR) AF: 0.250 AC: 11176 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3497 AN: 26134

East Asian (EAS) AF: 0.354 AC: 14051 AN: 39700

South Asian (SAS) AF: 0.105 AC: 9058 AN: 86252

European-Finnish (FIN) AF: 0.205 AC: 10928 AN: 53418

Middle Eastern (MID) AF: 0.134 AC: 771 AN: 5768

European-Non Finnish (NFE) AF: 0.158 AC: 175871 AN: 1111992

Other (OTH) AF: 0.181 AC: 10952 AN: 60394

GnomAD4 genome AF: 0.207 AC: 31464 AN: 152130 Hom.: 3651 Cov.: 32 AF XY: 0.205 AC XY: 15267 AN XY: 74368

African (AFR) AF: 0.286 AC: 11879 AN: 41502

American (AMR) AF: 0.211 AC: 3228 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 469 AN: 3472

East Asian (EAS) AF: 0.388 AC: 1997 AN: 5146

South Asian (SAS) AF: 0.105 AC: 509 AN: 4832

European-Finnish (FIN) AF: 0.198 AC: 2096 AN: 10582

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10766 AN: 67982

Other (OTH) AF: 0.188 AC: 398 AN: 2112

Alfa AF: 0.172 Hom.: 5938

Bravo AF: 0.214

TwinsUK AF: 0.169 AC: 625

ALSPAC AF: 0.156 AC: 601

ESP6500AA AF: 0.291 AC: 1280

ESP6500EA AF: 0.159 AC: 1370

ExAC AF: 0.192 AC: 23328

Asia WGS AF: 0.241 AC: 839 AN: 3478

EpiCase AF: 0.157

EpiControl AF: 0.150

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.78
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.00046	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.35	N
PhyloP100		0.74
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.058
Sift	Benign	0.28	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.012
MPC		0.050
ClinPred		0.0048	T
GERP RS		-0.75
Varity_R		0.050
gMVP		0.12
Mutation Taster		=99/1	polymorphism (auto)

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: rs3828161; hg19: chr2-228882970; COSMIC: COSV60880175;