8-38143305-ATTTTTTTTTT-ATTTTTTT

Variant names:

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

Variant summary

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

The NM_000349.3(STAR):​c.*965_*967delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00021 (0 hom., cov: 0)
• Consequence: STAR NM_000349.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408
• 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_*967delAAA		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_*967delAAA		3_prime_UTR	Exon 7 of 7	ENSP00000276449.3	P49675
	ASH2L	ENST00000971637.1		c.*771_*773delTTT		3_prime_UTR	Exon 17 of 17	ENSP00000641696.1
	STAR	ENST00000971759.1		c.*965_*967delAAA		3_prime_UTR	Exon 7 of 7	ENSP00000641818.1

Frequencies

GnomAD3 genomes AF: 0.000205 AC: 22 AN: 107202 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000999

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000252

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00139

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000164

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000205 AC: 22 AN: 107220 Hom.: 0 Cov.: 0 AF XY: 0.000216 AC XY: 11 AN XY: 51028

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000997 AC: 3 AN: 30094

American (AMR) AF: 0.000191 AC: 2 AN: 10470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2572

East Asian (EAS) AF: 0.000253 AC: 1 AN: 3956

South Asian (SAS) AF: 0.00 AC: 0 AN: 3198

European-Finnish (FIN) AF: 0.00139 AC: 8 AN: 5762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.000164 AC: 8 AN: 48822

Other (OTH) AF: 0.00 AC: 0 AN: 1422

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.41

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11326306; hg19: chr8-38000823;