1-110064397-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006492.3(ALX3):c.594+190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,090 control chromosomes in the GnomAD database, including 33,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (33801 hom., cov: 32)
• Consequence: ALX3 NM_006492.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.253

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]

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-110064397-A-G is Benign according to our data. Variant chr1-110064397-A-G is described in ClinVar as [Benign]. Clinvar id is 1253184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALX3	NM_006492.3	c.594+190T>C		intron_variant		ENST00000647563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALX3	ENST00000647563.2	c.594+190T>C		intron_variant			NM_006492.3	P1
ALX3	ENST00000649954.1	c.165+190T>C		intron_variant
STRIP1	ENST00000473429.5	n.4214-8058A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100579 AN: 151972 Hom.: 33767 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.662 AC: 100668 AN: 152090 Hom.: 33801 Cov.: 32 AF XY: 0.666 AC XY: 49537 AN XY: 74356

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.628

Alfa AF: 0.622 Hom.: 10259

Bravo AF: 0.663

Asia WGS AF: 0.761 AC: 2643 AN: 3478

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.8
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1077580; hg19: chr1-110607019;