8-38143324-TG-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000349.3(STAR):c.*948del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: STAR NM_000349.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0360

Genes affected

STAR (HGNC:11359): (steroidogenic acute regulatory protein) The protein encoded by this gene plays a key role in the acute regulation of steroid hormone synthesis by enhancing the conversion of cholesterol into pregnenolone. This protein permits the cleavage of cholesterol into pregnenolone by mediating the transport of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane. Mutations in this gene are a cause of congenital lipoid adrenal hyperplasia (CLAH), also called lipoid CAH. A pseudogene of this gene is located on chromosome 13. [provided by RefSeq, Jul 2008]

ASH2L (HGNC:744): (ASH2 like, histone lysine methyltransferase complex subunit) Enables beta-catenin binding activity and transcription cis-regulatory region binding activity. Contributes to histone methyltransferase activity (H3-K4 specific). Involved in histone H3-K4 methylation; positive regulation of cell population proliferation; and response to estrogen. Acts upstream of or within cellular response to DNA damage stimulus. Located in nucleus. Part of MLL3/4 complex and Set1C/COMPASS complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAR	NM_000349.3	c.*948del		3_prime_UTR_variant	7/7	ENST00000276449.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAR	ENST00000276449.9	c.*948del		3_prime_UTR_variant	7/7	1	NM_000349.3	P1
ASH2L	ENST00000521808.5	c.*5-414del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 189 AN: 109204 Hom.: 0 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00158

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.000781

Gnomad EAS AF: 0.00177

Gnomad SAS AF: 0.000902

Gnomad FIN AF: 0.00373

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00114

Gnomad OTH AF: 0.00272

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00173 AC: 189 AN: 109316 Hom.: 0 Cov.: 23 AF XY: 0.00203 AC XY: 107 AN XY: 52642

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00437

Gnomad4 ASJ AF: 0.000781

Gnomad4 EAS AF: 0.00177

Gnomad4 SAS AF: 0.000906

Gnomad4 FIN AF: 0.00373

Gnomad4 NFE AF: 0.00114

Gnomad4 OTH AF: 0.00268

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital adrenal hyperplasia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886062900; hg19: chr8-38000842; COSMIC: COSV51701227;