1-243484619-C-T

Variant names:

• chr1-243484619-C-T
• rs2994329
• NM_006642.5:c.1986-4395C>T

Variant summary

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

The NM_006642.5(SDCCAG8):​c.1986-4395C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,128 control chromosomes in the GnomAD database, including 5,881 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 0.26 (5881 hom., cov: 33)
• Consequence: SDCCAG8 NM_006642.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	NM_006642.5	MANE Select	c.1986-4395C>T		intron	N/A	NP_006633.1
	SDCCAG8	NM_001350248.2		c.2082-4395C>T		intron	N/A	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.1692-4395C>T		intron	N/A	NP_001337178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.1986-4395C>T		intron	N/A	ENSP00000355499.3
	SDCCAG8	ENST00000435549.1	TSL:1	c.1089-4395C>T		intron	N/A	ENSP00000410200.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39803 AN: 152010 Hom.: 5844 Cov.: 33

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.262 AC: 39909 AN: 152128 Hom.: 5881 Cov.: 33 AF XY: 0.263 AC XY: 19556 AN XY: 74380

African (AFR) AF: 0.395 AC: 16377 AN: 41464

American (AMR) AF: 0.237 AC: 3618 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3468

East Asian (EAS) AF: 0.398 AC: 2055 AN: 5164

South Asian (SAS) AF: 0.189 AC: 914 AN: 4824

European-Finnish (FIN) AF: 0.212 AC: 2244 AN: 10586

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13388 AN: 68012

Other (OTH) AF: 0.247 AC: 521 AN: 2110

Alfa AF: 0.226 Hom.: 9162

Bravo AF: 0.275

Asia WGS AF: 0.290 AC: 1009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		-0.45
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: rs2994329; hg19: chr1-243647921;