1-243256053-C-T

Variant names:

• chr1-243256053-C-T
• rs768318766
• NM_006642.5:c.-121C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_006642.5(SDCCAG8):​c.-121C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 914,336 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (1 hom.)
• Consequence: SDCCAG8 NM_006642.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 1.90
• Publications: 1 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):

• 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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0005 (381/762114) while in subpopulation NFE AF = 0.000747 (355/475328). AF 95% confidence interval is 0.000683. There are 1 homozygotes in GnomAdExome4. There are 183 alleles in the male GnomAdExome4 subpopulation. Median coverage is 11. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	NM_006642.5	MANE Select	c.-121C>T		5_prime_UTR	Exon 1 of 18	NP_006633.1	Q86SQ7-1
	SDCCAG8	NM_001350248.2		c.-121C>T		5_prime_UTR	Exon 1 of 19	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.-428C>T		5_prime_UTR	Exon 1 of 18	NP_001337178.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.-121C>T		5_prime_UTR	Exon 1 of 18	ENSP00000355499.3	Q86SQ7-1
	SDCCAG8	ENST00000951623.1		c.-121C>T		5_prime_UTR	Exon 1 of 18	ENSP00000621682.1
	SDCCAG8	ENST00000884079.1		c.-121C>T		5_prime_UTR	Exon 1 of 17	ENSP00000554138.1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000500 AC: 381 AN: 762114 Hom.: 1 Cov.: 11 AF XY: 0.000451 AC XY: 183 AN XY: 405994

African (AFR) AF: 0.0000499 AC: 1 AN: 20034

American (AMR) AF: 0.0000230 AC: 1 AN: 43450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21698

East Asian (EAS) AF: 0.00 AC: 0 AN: 36508

South Asian (SAS) AF: 0.00 AC: 0 AN: 72194

European-Finnish (FIN) AF: 0.000234 AC: 12 AN: 51280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4230

European-Non Finnish (NFE) AF: 0.000747 AC: 355 AN: 475328

Other (OTH) AF: 0.000321 AC: 12 AN: 37392

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18 AN XY: 74358

African (AFR) AF: 0.0000482 AC: 2 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000617 AC: 42 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000529 Hom.: 0

Bravo AF: 0.000329

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Bardet-Biedl syndrome 16 (1)
-	1	-	Senior-Loken syndrome 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.88
PhyloP100		1.9
PromoterAI		0.12	Neutral
Mutation Taster		=298/2	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs768318766; hg19: chr1-243419355;