1-110060664-A-AGGTGCTTCCTCCGTGGTGTCCAGGCAGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006492.3(ALX3):c.*68_*69insCCTGCCTGGACACCACGGAGGAAGCACC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,364,290 control chromosomes in the GnomAD database, including 249,236 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33855 hom., cov: 0)
  • Exomes 𝑓: 0.59 (215381 hom.)
• Consequence: ALX3 NM_006492.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.221

Genes affected

ALX3 (HGNC:449): (ALX homeobox 3) This gene encodes a nuclear protein with a homeobox DNA-binding domain that functions as a transcriptional regulator involved in cell-type differentiation and development. Preferential methylation of this gene's promoter is associated with advanced-stage neuroblastoma tumors. [provided by RefSeq, Jul 2008]

(HGNC:):

STRIP1 (HGNC:25916): (striatin interacting protein 1) This gene encodes a member of the striatin-interacting phosphatase and kinase complex, which is involved in localization of the Golgi body. The encoded protein participates in cytosketelal organization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-110060664-A-AGGTGCTTCCTCCGTGGTGTCCAGGCAGG is Benign according to our data. Variant chr1-110060664-A-AGGTGCTTCCTCCGTGGTGTCCAGGCAGG is described in ClinVar as [Benign]. Clinvar id is 1239551.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALX3	NM_006492.3	c.*68_*69insCCTGCCTGGACACCACGGAGGAAGCACC		3_prime_UTR_variant	4/4	ENST00000647563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALX3	ENST00000647563.2	c.*68_*69insCCTGCCTGGACACCACGGAGGAAGCACC		3_prime_UTR_variant	4/4		NM_006492.3	P1
	ENST00000554749.1	n.2329_2330insCTTCCTCCGTGGTGTCCAGGCAGGGGTG		non_coding_transcript_exon_variant	1/1
ALX3	ENST00000649954.1	c.*68_*69insCCTGCCTGGACACCACGGAGGAAGCACC		3_prime_UTR_variant	3/3
STRIP1	ENST00000473429.5	n.4213+5866_4213+5867insCTTCCTCCGTGGTGTCCAGGCAGGGGTG		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100216 AN: 151606 Hom.: 33808 Cov.: 0

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.627

GnomAD4 exome AF: 0.590 AC: 715067 AN: 1212568 Hom.: 215381 Cov.: 26 AF XY: 0.592 AC XY: 354664 AN XY: 598886

Gnomad4 AFR exome AF: 0.779

Gnomad4 AMR exome AF: 0.699

Gnomad4 ASJ exome AF: 0.590

Gnomad4 EAS exome AF: 0.822

Gnomad4 SAS exome AF: 0.719

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.560

Gnomad4 OTH exome AF: 0.604

GnomAD4 genome AF: 0.661 AC: 100318 AN: 151722 Hom.: 33855 Cov.: 0 AF XY: 0.666 AC XY: 49387 AN XY: 74144

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.630

Alfa AF: 0.334 Hom.: 758

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

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: rs144523285; hg19: chr1-110603286;