dbSNP rs547776191: SDCCAG8:c.-130C>A (chr1-243256044-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_006642.5(SDCCAG8):c.-130C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000688 in 855,582 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 0.00068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00069 ( 1 hom. )

Consequence

SDCCAG8
NM_006642.5 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.402

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000683 (104/152304) while in subpopulation NFE AF = 0.00121 (82/67998). AF 95% confidence interval is 0.000996. There are 0 homozygotes in GnomAd4. There are 47 alleles in the male GnomAd4 subpopulation. Median coverage is 33. 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SDCCAG8	NM_006642.5	MANE Select	c.-130C>A	5_prime_UTR	Exon 1 of 18	NP_006633.1	Q86SQ7-1
SDCCAG8	NM_001350248.2		c.-130C>A	5_prime_UTR	Exon 1 of 19	NP_001337177.1
SDCCAG8	NM_001350249.2		c.-437C>A	5_prime_UTR	Exon 1 of 18	NP_001337178.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.-130C>A	5_prime_UTR	Exon 1 of 18	ENSP00000355499.3	Q86SQ7-1
SDCCAG8	ENST00000951623.1		c.-130C>A	5_prime_UTR	Exon 1 of 18	ENSP00000621682.1
SDCCAG8	ENST00000884079.1		c.-130C>A	5_prime_UTR	Exon 1 of 17	ENSP00000554138.1

Frequencies

GnomAD3 genomes

AF:

0.000683

AC:

104

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.000523

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:

0.00121

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000690

AC:

485

AN:

703278

Hom.:

Cov.:

AF XY:

0.000667

AC XY:

252

AN XY:

377772

show subpopulations

African (AFR)

AF:

0.000212

AC:

AN:

18906

American (AMR)

AF:

0.000235

AC:

AN:

42624

Ashkenazi Jewish (ASJ)

AF:

0.0000473

AC:

AN:

21152

East Asian (EAS)

AF:

0.00

AC:

AN:

35998

South Asian (SAS)

AF:

0.00

AC:

AN:

70688

European-Finnish (FIN)

AF:

0.0000797

AC:

AN:

50204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4002

European-Non Finnish (NFE)

AF:

0.00105

AC:

444

AN:

424190

Other (OTH)

AF:

0.000619

AC:

AN:

35514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

114

143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000683

AC:

104

AN:

152304

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41586

American (AMR)

AF:

0.000523

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00121

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000212

Hom.:

Bravo

AF:

0.000676

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bardet-Biedl syndrome 16 (1)

Senior-Loken syndrome 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.40

PromoterAI

0.11

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over