1-236550992-T-TAAA

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_201544.4(LGALS8):​c.*2847_*2849dupAAA 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 0.0013 (1 hom., cov: 0)
  • Exomes 𝑓: 0.016 (8 hom.)
• Consequence: LGALS8 NM_201544.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

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_*2849dupAAA		3_prime_UTR	Exon 10 of 10	NP_963838.1
	HEATR1	NM_018072.6	MANE Select	c.6347-5_6347-3dupTTT		splice_region intron	N/A	NP_060542.4
	LGALS8	NM_006499.5		c.*2847_*2849dupAAA		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_*2849dupAAA		3_prime_UTR	Exon 10 of 10	ENSP00000355543.4
	LGALS8	ENST00000450372.6	TSL:1	c.*2847_*2849dupAAA		3_prime_UTR	Exon 12 of 12	ENSP00000408657.2
	HEATR1	ENST00000366582.8	TSL:5 MANE Select	c.6347-5_6347-3dupTTT		splice_region intron	N/A	ENSP00000355541.3

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 173 AN: 137752 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00160

Gnomad ASJ AF: 0.000602

Gnomad EAS AF: 0.00169

Gnomad SAS AF: 0.00475

Gnomad FIN AF: 0.00162

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.000541

GnomAD2 exomes AF: 0.0171 AC: 1150 AN: 67430 AF XY: 0.0161

Gnomad AFR exome AF: 0.00656

Gnomad AMR exome AF: 0.0162

Gnomad ASJ exome AF: 0.0149

Gnomad EAS exome AF: 0.0195

Gnomad FIN exome AF: 0.0124

Gnomad NFE exome AF: 0.0209

Gnomad OTH exome AF: 0.0213

GnomAD4 exome AF: 0.0162 AC: 18021 AN: 1110106 Hom.: 8 Cov.: 18 AF XY: 0.0156 AC XY: 8612 AN XY: 552284

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

African (AFR) AF: 0.00604 AC: 157 AN: 25988

American (AMR) AF: 0.0126 AC: 297 AN: 23576

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 200 AN: 18914

East Asian (EAS) AF: 0.00847 AC: 288 AN: 33986

South Asian (SAS) AF: 0.0127 AC: 771 AN: 60516

European-Finnish (FIN) AF: 0.0114 AC: 354 AN: 30992

Middle Eastern (MID) AF: 0.00748 AC: 29 AN: 3876

European-Non Finnish (NFE) AF: 0.0177 AC: 15300 AN: 864530

Other (OTH) AF: 0.0131 AC: 625 AN: 47728

⚠️ 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 AF: 0.00126 AC: 173 AN: 137772 Hom.: 1 Cov.: 0 AF XY: 0.00120 AC XY: 79 AN XY: 65754

African (AFR) AF: 0.00117 AC: 44 AN: 37756

American (AMR) AF: 0.00160 AC: 22 AN: 13756

Ashkenazi Jewish (ASJ) AF: 0.000602 AC: 2 AN: 3322

East Asian (EAS) AF: 0.00170 AC: 8 AN: 4716

South Asian (SAS) AF: 0.00477 AC: 20 AN: 4192

European-Finnish (FIN) AF: 0.00162 AC: 11 AN: 6810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00101 AC: 65 AN: 64234

Other (OTH) AF: 0.000538 AC: 1 AN: 1860

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs55866014; hg19: chr1-236714292;