NM_000349.3:c.*962_*963dupAA

Variant names:

• chr8-38143305-A-ATT
• rs11326306
• NM_000349.3:c.*966_*967dupAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000349.3(STAR):​c.*966_*967dupAA 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 0.0048 (9 hom., cov: 0)
• Consequence: STAR NM_000349.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00477 (512/107240) while in subpopulation AFR AF = 0.0147 (441/30088). AF 95% confidence interval is 0.0135. There are 9 homozygotes in GnomAd4. There are 233 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.*966_*967dupAA		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.*966_*967dupAA		3_prime_UTR	Exon 7 of 7	ENSP00000276449.3	P49675
	ASH2L	ENST00000971637.1		c.*772_*773dupTT		3_prime_UTR	Exon 17 of 17	ENSP00000641696.1
	STAR	ENST00000971759.1		c.*966_*967dupAA		3_prime_UTR	Exon 7 of 7	ENSP00000641818.1

Frequencies

GnomAD3 genomes AF: 0.00477 AC: 511 AN: 107222 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00363

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00176

Gnomad SAS AF: 0.000311

Gnomad FIN AF: 0.000867

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000184

Gnomad OTH AF: 0.00845

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

GnomAD4 genome AF: 0.00477 AC: 512 AN: 107240 Hom.: 9 Cov.: 0 AF XY: 0.00457 AC XY: 233 AN XY: 51028

African (AFR) AF: 0.0147 AC: 441 AN: 30088

American (AMR) AF: 0.00353 AC: 37 AN: 10468

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

East Asian (EAS) AF: 0.00177 AC: 7 AN: 3956

South Asian (SAS) AF: 0.000313 AC: 1 AN: 3198

European-Finnish (FIN) AF: 0.000867 AC: 5 AN: 5770

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

European-Non Finnish (NFE) AF: 0.000184 AC: 9 AN: 48842

Other (OTH) AF: 0.00844 AC: 12 AN: 1422

Alfa AF: 0.00 Hom.: 1101

ClinVar

Not reported in ClinVar

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

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;