rs12145833

Variant names:

• chr1-243320452-T-G
• rs12145833
• NM_006642.5:c.1068+3559T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006642.5(SDCCAG8):​c.1068+3559T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,210 control chromosomes in the GnomAD database, including 1,233 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 0.11 (1233 hom., cov: 32)
• Consequence: SDCCAG8 NM_006642.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 18 publications found

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):

• Senior-Loken syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Bardet-Biedl syndrome 16

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDCCAG8	NM_006642.5	c.1068+3559T>G		intron_variant	Intron 9 of 17	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.1068+3559T>G		intron_variant	Intron 9 of 17	1	NM_006642.5	ENSP00000355499.3
SDCCAG8	ENST00000435549.1	c.408+3559T>G		intron_variant	Intron 4 of 10	1		ENSP00000410200.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17288 AN: 152092 Hom.: 1232 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0670

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.114 AC: 17289 AN: 152210 Hom.: 1233 Cov.: 32 AF XY: 0.112 AC XY: 8353 AN XY: 74428

African (AFR) AF: 0.0385 AC: 1601 AN: 41536

American (AMR) AF: 0.132 AC: 2018 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3466

East Asian (EAS) AF: 0.0670 AC: 347 AN: 5180

South Asian (SAS) AF: 0.108 AC: 521 AN: 4822

European-Finnish (FIN) AF: 0.132 AC: 1396 AN: 10598

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10484 AN: 67994

Other (OTH) AF: 0.112 AC: 237 AN: 2112

Alfa AF: 0.111 Hom.: 544

Bravo AF: 0.111

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.68
PhyloP100		-1.2
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: rs12145833; hg19: chr1-243483754;