rs3811515

Variant names:

• chr2-228018313-A-C
• rs3811515
• NM_001142644.2:c.2541T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-228018313-A-C
• chr2-228018313-A-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.2541T>G​(p.His847Gln) 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 1,613,900 control chromosomes in the GnomAD database, including 54,530 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 0.20 (3960 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50570 hom.)
• Consequence: SPHKAP NM_001142644.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 21 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=3.0601025E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPHKAP	NM_001142644.2	c.2541T>G	p.His847Gln	missense_variant	Exon 7 of 12	ENST00000392056.8	NP_001136116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPHKAP	ENST00000392056.8	c.2541T>G	p.His847Gln	missense_variant	Exon 7 of 12	1	NM_001142644.2	ENSP00000375909.3
SPHKAP	ENST00000344657.5	c.2541T>G	p.His847Gln	missense_variant	Exon 7 of 11	1		ENSP00000339886.5

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30667 AN: 151926 Hom.: 3954 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.221

GnomAD2 exomes AF: 0.266 AC: 66825 AN: 251402 AF XY: 0.274

Gnomad AFR exome AF: 0.0525

Gnomad AMR exome AF: 0.335

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.216

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.252

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.256 AC: 373743 AN: 1461854 Hom.: 50570 Cov.: 62 AF XY: 0.261 AC XY: 189917 AN XY: 727232

African (AFR) AF: 0.0464 AC: 1552 AN: 33480

American (AMR) AF: 0.327 AC: 14636 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6967 AN: 26136

East Asian (EAS) AF: 0.268 AC: 10635 AN: 39700

South Asian (SAS) AF: 0.424 AC: 36573 AN: 86256

European-Finnish (FIN) AF: 0.197 AC: 10515 AN: 53416

Middle Eastern (MID) AF: 0.285 AC: 1641 AN: 5766

European-Non Finnish (NFE) AF: 0.249 AC: 276762 AN: 1111982

Other (OTH) AF: 0.239 AC: 14462 AN: 60396

GnomAD4 genome AF: 0.202 AC: 30677 AN: 152046 Hom.: 3960 Cov.: 32 AF XY: 0.206 AC XY: 15272 AN XY: 74290

African (AFR) AF: 0.0565 AC: 2344 AN: 41502

American (AMR) AF: 0.293 AC: 4469 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 941 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1141 AN: 5150

South Asian (SAS) AF: 0.429 AC: 2064 AN: 4812

European-Finnish (FIN) AF: 0.192 AC: 2033 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16698 AN: 67968

Other (OTH) AF: 0.221 AC: 465 AN: 2106

Alfa AF: 0.236 Hom.: 17203

Bravo AF: 0.199

TwinsUK AF: 0.240 AC: 890

ALSPAC AF: 0.248 AC: 954

ESP6500AA AF: 0.0640 AC: 282

ESP6500EA AF: 0.252 AC: 2167

ExAC AF: 0.264 AC: 32077

Asia WGS AF: 0.335 AC: 1165 AN: 3478

EpiCase AF: 0.247

EpiControl AF: 0.260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.69
DANN	Benign	0.78
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.41	T;T
MetaRNN	Benign	0.00031	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L;L
PhyloP100		0.23
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.10
Sift	Benign	0.13	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.011	B;B
Vest4		0.025
MutPred		0.025		Loss of glycosylation at P846 (P = 0.1735);Loss of glycosylation at P846 (P = 0.1735);
MPC		0.049
ClinPred		0.0034	T
GERP RS		0.98
Varity_R		0.052
gMVP		0.14
Mutation Taster		=98/2	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: rs3811515; hg19: chr2-228883029; COSMIC: COSV60870915;