1-236550992-TAAA-T

Variant names:

• chr1-236550992-TAAA-T
• rs55866014
• NM_201544.4:c.*2847_*2849delAAA

Variant summary

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

The NM_201544.4(LGALS8):​c.*2847_*2849delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000596 in 1,115,326 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00060 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LGALS8 NM_201544.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

Genes affected

LGALS8 (HGNC:6569): (galectin 8) This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains. The galectins have been implicated in many essential functions including development, differentiation, cell-cell adhesion, cell-matrix interaction, growth regulation, apoptosis, and RNA splicing. This gene is widely expressed in tumoral tissues and seems to be involved in integrin-like cell interactions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

HEATR1 (HGNC:25517): (HEAT repeat containing 1) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in fibrillar center and mitochondrion. Implicated in pancreatic ductal carcinoma. Biomarker of glioblastoma. [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_201544.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	NM_201544.4	MANE Select	c.*2847_*2849delAAA		3_prime_UTR	Exon 10 of 10	NP_963838.1
	HEATR1	NM_018072.6	MANE Select	c.6347-5_6347-3delTTT		splice_region intron	N/A	NP_060542.4
	LGALS8	NM_006499.5		c.*2847_*2849delAAA		3_prime_UTR	Exon 12 of 12	NP_006490.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	ENST00000366584.9	TSL:1 MANE Select	c.*2847_*2849delAAA		3_prime_UTR	Exon 10 of 10	ENSP00000355543.4
	LGALS8	ENST00000450372.6	TSL:1	c.*2847_*2849delAAA		3_prime_UTR	Exon 12 of 12	ENSP00000408657.2
	HEATR1	ENST00000366582.8	TSL:5 MANE Select	c.6347-5_6347-3delTTT		splice_region intron	N/A	ENSP00000355541.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 137782 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000596 AC: 665 AN: 1115326 Hom.: 0 AF XY: 0.000645 AC XY: 358 AN XY: 554848

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

African (AFR) AF: 0.000615 AC: 16 AN: 26014

American (AMR) AF: 0.00182 AC: 43 AN: 23676

Ashkenazi Jewish (ASJ) AF: 0.000844 AC: 16 AN: 18962

East Asian (EAS) AF: 0.000615 AC: 21 AN: 34142

South Asian (SAS) AF: 0.000970 AC: 59 AN: 60812

European-Finnish (FIN) AF: 0.0000962 AC: 3 AN: 31188

Middle Eastern (MID) AF: 0.000773 AC: 3 AN: 3880

European-Non Finnish (NFE) AF: 0.000548 AC: 476 AN: 868690

Other (OTH) AF: 0.000584 AC: 28 AN: 47962

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 137782 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 65728

African (AFR) AF: 0.00 AC: 0 AN: 37692

American (AMR) AF: 0.00 AC: 0 AN: 13746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3322

East Asian (EAS) AF: 0.00 AC: 0 AN: 4736

South Asian (SAS) AF: 0.00 AC: 0 AN: 4208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64256

Other (OTH) AF: 0.00 AC: 0 AN: 1852

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs55866014; hg19: chr1-236714292;