2-228022957-T-C

Variant names:

• chr2-228022957-T-C
• rs6736430
• NM_001142644.2:c.442-991A>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.442-991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,968 control chromosomes in the GnomAD database, including 11,543 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11543 hom., cov: 32)
• Consequence: SPHKAP NM_001142644.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 4 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 (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 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.442-991A>G		intron	N/A	NP_001136116.1	Q2M3C7-1
	SPHKAP	NM_030623.4		c.442-991A>G		intron	N/A	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.442-991A>G		intron	N/A	ENSP00000375909.3	Q2M3C7-1
	SPHKAP	ENST00000344657.5	TSL:1	c.442-991A>G		intron	N/A	ENSP00000339886.5	Q2M3C7-2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58018 AN: 151848 Hom.: 11517 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.388

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.382 AC: 58094 AN: 151968 Hom.: 11543 Cov.: 32 AF XY: 0.385 AC XY: 28584 AN XY: 74280

African (AFR) AF: 0.461 AC: 19105 AN: 41436

American (AMR) AF: 0.432 AC: 6594 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1468 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1155 AN: 5168

South Asian (SAS) AF: 0.506 AC: 2438 AN: 4816

European-Finnish (FIN) AF: 0.294 AC: 3103 AN: 10550

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22808 AN: 67952

Other (OTH) AF: 0.387 AC: 816 AN: 2110

Alfa AF: 0.363 Hom.: 1550

Bravo AF: 0.392

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.8
DANN	Benign	0.85
PhyloP100		-0.0020
Mutation Taster		=100/0	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: rs6736430; hg19: chr2-228887673;