Genetic Variant SPHKAP:c.247-30786C>A (chr2-228058329-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142644.2(SPHKAP):c.247-30786C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,088 control chromosomes in the GnomAD database, including 34,474 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 0.67 ( 34474 hom., cov: 32)

Consequence

SPHKAP
NM_001142644.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.311

Publications

2 publications found

Variant links:

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]

SPHKAP links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001142644.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 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.247-30786C>A		intron	N/A	NP_001136116.1	Q2M3C7-1
	SPHKAP	NM_030623.4		c.247-30786C>A		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.247-30786C>A		intron	N/A	ENSP00000375909.3	Q2M3C7-1
	SPHKAP	ENST00000344657.5	TSL:1	c.247-30786C>A		intron	N/A	ENSP00000339886.5	Q2M3C7-2

Frequencies

GnomAD3 genomes

AF:

0.670

AC:

101801

AN:

151970

Hom.:

34415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.775

Gnomad AMI

AF:

0.819

Gnomad AMR

AF:

0.693

Gnomad ASJ

AF:

0.697

Gnomad EAS

AF:

0.646

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.599

Gnomad OTH

AF:

0.669

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

GnomAD4 genome

AF:

0.670

AC:

101927

AN:

152088

Hom.:

34474

Cov.:

AF XY:

0.673

AC XY:

50046

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.775

AC:

32163

AN:

41496

American (AMR)

AF:

0.693

AC:

10591

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.697

AC:

2417

AN:

3468

East Asian (EAS)

AF:

0.646

AC:

3342

AN:

5176

South Asian (SAS)

AF:

0.731

AC:

3524

AN:

4824

European-Finnish (FIN)

AF:

0.646

AC:

6826

AN:

10562

Middle Eastern (MID)

AF:

0.677

AC:

199

AN:

294

European-Non Finnish (NFE)

AF:

0.599

AC:

40700

AN:

67968

Other (OTH)

AF:

0.672

AC:

1421

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1704

3408

5112

6816

8520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.625

Hom.:

14879

Bravo

AF:

0.675

Asia WGS

AF:

0.729

AC:

2534

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.98

(source)

DANN

Benign

0.18

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over