Genetic Variant SDCCAG8:c.1221+4318T>C (chr1-243335010-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006642.5(SDCCAG8):c.1221+4318T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,952 control chromosomes in the GnomAD database, including 18,735 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 0.47 ( 18735 hom., cov: 31)

Consequence

SDCCAG8
NM_006642.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.29

Publications

11 publications found

Variant links:

Genes affected

SDCCAG8 (HGNC:10671): (SHH signaling and ciliogenesis regulator SDCCAG8) This gene encodes a centrosome associated protein. This protein may be involved in organizing the centrosome during interphase and mitosis. Mutations in this gene are associated with retinal-renal ciliopathy. [provided by RefSeq, Oct 2010]

SDCCAG8 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 16
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp
Senior-Loken syndrome 7
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
ciliopathy
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SDCCAG8 links:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006642.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SDCCAG8	NM_006642.5	MANE Select	c.1221+4318T>C	intron	N/A	NP_006633.1	Q86SQ7-1
SDCCAG8	NM_001350248.2		c.1317+4318T>C	intron	N/A	NP_001337177.1
SDCCAG8	NM_001350249.2		c.927+4318T>C	intron	N/A	NP_001337178.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.1221+4318T>C	intron	N/A	ENSP00000355499.3	Q86SQ7-1
SDCCAG8	ENST00000435549.1	TSL:1	c.561+4318T>C	intron	N/A	ENSP00000410200.1	A0A0C4DG71
SDCCAG8	ENST00000884080.1		c.1317+4318T>C	intron	N/A	ENSP00000554139.1

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71541

AN:

151834

Hom.:

18717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.599

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.743

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.619

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.547

Gnomad OTH

AF:

0.503

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

GnomAD4 genome

AF:

0.471

AC:

71572

AN:

151952

Hom.:

18735

Cov.:

AF XY:

0.475

AC XY:

35319

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.230

AC:

9551

AN:

41452

American (AMR)

AF:

0.600

AC:

9147

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1797

AN:

3470

East Asian (EAS)

AF:

0.743

AC:

3841

AN:

5168

South Asian (SAS)

AF:

0.395

AC:

1904

AN:

4816

European-Finnish (FIN)

AF:

0.619

AC:

6523

AN:

10546

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.547

AC:

37177

AN:

67940

Other (OTH)

AF:

0.507

AC:

1067

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1760

3519

5279

7038

8798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<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:

0.522

Hom.:

91501

Bravo

AF:

0.460

Asia WGS

AF:

0.551

AC:

1917

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.1

(source)

DANN

Benign

0.64

PhyloP100

2.3

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

Publications

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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