8-38143305-ATTTTTTTTTT-ATTTTTTTTTTTTT

Variant names:

• chr8-38143305-A-ATTT
• rs11326306
• NM_000349.3:c.*965_*967dupAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000349.3(STAR):​c.*965_*967dupAAA 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 0.033 (185 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: STAR NM_000349.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.97
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000349.3. 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
	STAR	NM_000349.3	MANE Select	c.*965_*967dupAAA		3_prime_UTR	Exon 7 of 7	NP_000340.2	Q6IBK0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAR	ENST00000276449.9	TSL:1 MANE Select	c.*965_*967dupAAA		3_prime_UTR	Exon 7 of 7	ENSP00000276449.3	P49675
	ASH2L	ENST00000971637.1		c.*771_*773dupTTT		3_prime_UTR	Exon 17 of 17	ENSP00000641696.1
	STAR	ENST00000971759.1		c.*965_*967dupAAA		3_prime_UTR	Exon 7 of 7	ENSP00000641818.1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 3547 AN: 107150 Hom.: 185 Cov.: 0

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.00233

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0252

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.0214

Gnomad NFE AF: 0.00493

Gnomad OTH AF: 0.0303

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: 0.0331 AC: 3552 AN: 107164 Hom.: 185 Cov.: 0 AF XY: 0.0386 AC XY: 1969 AN XY: 50984

African (AFR) AF: 0.0273 AC: 822 AN: 30072

American (AMR) AF: 0.0823 AC: 860 AN: 10444

Ashkenazi Jewish (ASJ) AF: 0.00233 AC: 6 AN: 2572

East Asian (EAS) AF: 0.260 AC: 1028 AN: 3950

South Asian (SAS) AF: 0.0253 AC: 81 AN: 3196

European-Finnish (FIN) AF: 0.0809 AC: 465 AN: 5748

Middle Eastern (MID) AF: 0.0234 AC: 5 AN: 214

European-Non Finnish (NFE) AF: 0.00493 AC: 241 AN: 48838

Other (OTH) AF: 0.0310 AC: 44 AN: 1420

Alfa AF: 0.0240 Hom.: 1101

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital adrenal hyperplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs11326306; hg19: chr8-38000823;