rs3811514

Variant names:

• chr2-228019005-T-C
• rs3811514
• NM_001142644.2:c.1849A>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.1849A>G​(p.Lys617Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,613,484 control chromosomes in the GnomAD database, including 225,334 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 0.59 (26964 hom., cov: 32)
  • Exomes 𝑓: 0.52 (198370 hom.)
• Consequence: SPHKAP NM_001142644.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 33 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=1.3734482E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPHKAP	NM_001142644.2	c.1849A>G	p.Lys617Glu	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.1849A>G	p.Lys617Glu	missense_variant	Exon 7 of 12	1	NM_001142644.2	ENSP00000375909.3
SPHKAP	ENST00000344657.5	c.1849A>G	p.Lys617Glu	missense_variant	Exon 7 of 11	1		ENSP00000339886.5

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88989 AN: 151966 Hom.: 26911 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.574

GnomAD2 exomes AF: 0.575 AC: 143356 AN: 249500 AF XY: 0.566

Gnomad AFR exome AF: 0.748

Gnomad AMR exome AF: 0.733

Gnomad ASJ exome AF: 0.553

Gnomad EAS exome AF: 0.626

Gnomad FIN exome AF: 0.515

Gnomad NFE exome AF: 0.496

Gnomad OTH exome AF: 0.543

GnomAD4 exome AF: 0.516 AC: 754541 AN: 1461400 Hom.: 198370 Cov.: 80 AF XY: 0.518 AC XY: 376850 AN XY: 726966

African (AFR) AF: 0.743 AC: 24854 AN: 33472

American (AMR) AF: 0.721 AC: 32180 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 14285 AN: 26132

East Asian (EAS) AF: 0.622 AC: 24688 AN: 39670

South Asian (SAS) AF: 0.616 AC: 53137 AN: 86250

European-Finnish (FIN) AF: 0.515 AC: 27487 AN: 53384

Middle Eastern (MID) AF: 0.606 AC: 3495 AN: 5768

European-Non Finnish (NFE) AF: 0.488 AC: 542222 AN: 1111724

Other (OTH) AF: 0.533 AC: 32193 AN: 60374

GnomAD4 genome AF: 0.586 AC: 89104 AN: 152084 Hom.: 26964 Cov.: 32 AF XY: 0.587 AC XY: 43659 AN XY: 74328

African (AFR) AF: 0.739 AC: 30668 AN: 41504

American (AMR) AF: 0.636 AC: 9728 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1935 AN: 3468

East Asian (EAS) AF: 0.613 AC: 3163 AN: 5158

South Asian (SAS) AF: 0.620 AC: 2990 AN: 4824

European-Finnish (FIN) AF: 0.493 AC: 5199 AN: 10544

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33479 AN: 67982

Other (OTH) AF: 0.573 AC: 1213 AN: 2116

Alfa AF: 0.529 Hom.: 74513

Bravo AF: 0.602

TwinsUK AF: 0.494 AC: 1830

ALSPAC AF: 0.482 AC: 1857

ESP6500AA AF: 0.737 AC: 3248

ESP6500EA AF: 0.499 AC: 4291

ExAC AF: 0.572 AC: 69395

Asia WGS AF: 0.645 AC: 2242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.5
DANN	Benign	0.16
DEOGEN2	Benign	0.016	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.042	T;T
MetaRNN	Benign	0.0000014	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.4	N;N
PhyloP100		1.5
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.5	N;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.027
ClinPred		0.0019	T
GERP RS		4.0
Varity_R		0.070
gMVP		0.31
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: rs3811514; hg19: chr2-228883721; COSMIC: COSV60870928;