Genetic Variant LGALS8:c.*2846_*2849dupAAAA (chr1-236550992-T-TAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_201544.4(LGALS8):c.*2846_*2849dupAAAA 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 0.00010 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00075 ( 0 hom. )

Consequence

LGALS8
NM_201544.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.486

Publications

1 publications found

Variant links:

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]

LGALS8 links:

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]

HEATR1 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LGALS8	NM_201544.4	MANE Select	c.2846_2849dupAAAA	3_prime_UTR	Exon 10 of 10	NP_963838.1
HEATR1	NM_018072.6	MANE Select	c.6347-6_6347-3dupTTTT	splice_region intron	N/A	NP_060542.4
LGALS8	NM_006499.5		c.2846_2849dupAAAA	3_prime_UTR	Exon 12 of 12	NP_006490.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LGALS8	ENST00000366584.9	TSL:1 MANE Select	c.2846_2849dupAAAA	3_prime_UTR	Exon 10 of 10	ENSP00000355543.4
LGALS8	ENST00000450372.6	TSL:1	c.2846_2849dupAAAA	3_prime_UTR	Exon 12 of 12	ENSP00000408657.2
HEATR1	ENST00000366582.8	TSL:5 MANE Select	c.6347-6_6347-3dupTTTT	splice_region intron	N/A	ENSP00000355541.3

Frequencies

GnomAD3 genomes

AF:

0.000102

AC:

AN:

137786

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000238

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000171

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000754

AC:

842

AN:

1116538

Hom.:

Cov.:

AF XY:

0.000722

AC XY:

401

AN XY:

555592

show subpopulations

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

African (AFR)

AF:

0.000307

AC:

AN:

26078

American (AMR)

AF:

0.000548

AC:

AN:

23740

Ashkenazi Jewish (ASJ)

AF:

0.000736

AC:

AN:

19022

East Asian (EAS)

AF:

0.000322

AC:

AN:

34212

South Asian (SAS)

AF:

0.000377

AC:

AN:

61084

European-Finnish (FIN)

AF:

0.000320

AC:

AN:

31226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3892

European-Non Finnish (NFE)

AF:

0.000836

AC:

727

AN:

869262

Other (OTH)

AF:

0.000750

AC:

AN:

48022

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.282

Heterozygous variant carriers

164

247

329

411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000102

AC:

AN:

137806

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

65774

show subpopulations

African (AFR)

AF:

0.0000530

AC:

AN:

37760

American (AMR)

AF:

0.00

AC:

AN:

13760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3322

East Asian (EAS)

AF:

0.00

AC:

AN:

4716

South Asian (SAS)

AF:

0.000239

AC:

AN:

4192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.000171

AC:

AN:

64244

Other (OTH)

AF:

0.00

AC:

AN:

1862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.49

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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1-236550992-TAAAAAAAAA-TAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over