ENST00000450372.6:c.569A>C

Variant names:

• chr1-236542934-A-C
• rs35968435
• ENST00000450372.6:c.569A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000450372.6(LGALS8):​c.569A>C​(p.Asp190Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D190G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGALS8 ENST00000450372.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• Publications: 8 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]

ENSG00000230325 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17596358).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000450372.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	NM_201544.4	MANE Select	c.549+147A>C		intron	N/A	NP_963838.1	O00214-1
	LGALS8	NM_006499.5		c.569A>C	p.Asp190Ala	missense	Exon 9 of 12	NP_006490.3
	LGALS8	NM_201545.2		c.569A>C	p.Asp190Ala	missense	Exon 9 of 12	NP_963839.1	O00214-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	ENST00000450372.6	TSL:1	c.569A>C	p.Asp190Ala	missense	Exon 9 of 12	ENSP00000408657.2	O00214-2
	LGALS8	ENST00000525042.1	TSL:1	c.392A>C	p.Asp131Ala	missense	Exon 5 of 8	ENSP00000431884.1	F6V2D4
	LGALS8	ENST00000366584.9	TSL:1 MANE Select	c.549+147A>C		intron	N/A	ENSP00000355543.4	O00214-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 124

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.084
Sift	Benign	0.20	T
Sift4G	Benign	0.77	T
Polyphen		0.88	P
Vest4		0.51
MutPred		0.64		Gain of catalytic residue at D131 (P = 0.0103)
MVP		0.41
MPC		0.072
ClinPred		0.45	T
GERP RS		4.1
gMVP		0.36
Mutation Taster		=95/5	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: rs35968435; hg19: chr1-236706234;