chr1-236542934-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_006499.5(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. 12/18 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 NM_006499.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a mutagenesis_site Does not affect localization to cytoplasmic vesicles in case of infection by S.typhimurium. (size 0) in uniprot entity LEG8_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17596358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS8	NM_201544.4	c.549+147A>C		intron_variant	Intron 7 of 9	ENST00000366584.9	NP_963838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS8	ENST00000366584.9	c.549+147A>C		intron_variant	Intron 7 of 9	1	NM_201544.4	ENSP00000355543.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0089	.;.;T;.;T;.;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.36	.;.;T;.;T;T;.
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.48	N;N;N;N;N;N;N
REVEL	Benign	0.084
Sift	Benign	0.20	T;T;D;T;T;T;T
Sift4G	Benign	0.77	T;T;T;T;T;T;T
Polyphen		0.88	P;P;.;P;B;P;B
Vest4		0.51
MutPred		0.64		.;.;.;.;Gain of catalytic residue at D131 (P = 0.0103);.;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

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: rs35968435; hg19: chr1-236706234;