chr17-47853173-G-T

Variant names:

• chr17-47853173-G-T
• rs4794202
• ENST00000342234.3:c.-58+2481C>A

Variant summary

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

The NM_199262.3(SP6):​c.-58+2481C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,226 control chromosomes in the GnomAD database, including 1,515 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 0.13 (1515 hom., cov: 32)
• Consequence: SP6 NM_199262.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 9 publications found

Genes affected

SP6 (HGNC:14530): (Sp6 transcription factor) SP6 belongs to a family of transcription factors that contain 3 classical zinc finger DNA-binding domains consisting of a zinc atom tetrahedrally coordinated by 2 cysteines and 2 histidines (C2H2 motif). These transcription factors bind to GC-rich sequences and related GT and CACCC boxes (Scohy et al., 2000 [PubMed 11087666]).[supplied by OMIM, Mar 2008]

SP6 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta, IIa 1K

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199262.3. 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
	SP6	NM_199262.3		c.-58+2481C>A		intron	N/A	NP_954871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP6	ENST00000342234.3	TSL:1	c.-58+2481C>A		intron	N/A	ENSP00000340799.2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20023 AN: 152108 Hom.: 1516 Cov.: 32

Gnomad AFR AF: 0.0764

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.132 AC: 20035 AN: 152226 Hom.: 1515 Cov.: 32 AF XY: 0.132 AC XY: 9837 AN XY: 74442

African (AFR) AF: 0.0764 AC: 3175 AN: 41540

American (AMR) AF: 0.157 AC: 2400 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3468

East Asian (EAS) AF: 0.0545 AC: 283 AN: 5194

South Asian (SAS) AF: 0.175 AC: 844 AN: 4818

European-Finnish (FIN) AF: 0.128 AC: 1352 AN: 10598

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10949 AN: 67986

Other (OTH) AF: 0.163 AC: 344 AN: 2112

Alfa AF: 0.144 Hom.: 2873

Bravo AF: 0.131

Asia WGS AF: 0.107 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.70
PhyloP100		0.21
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: rs4794202; hg19: chr17-45930539;