1-236538910-A-C

Variant names:

• chr1-236538910-A-C
• rs1041937
• NM_201544.4:c.166A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_201544.4(LGALS8):​c.166A>C​(p.Met56Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGALS8 NM_201544.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 28 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022184819).

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.166A>C	p.Met56Leu	missense	Exon 4 of 10	NP_963838.1
	LGALS8	NM_006499.5		c.166A>C	p.Met56Leu	missense	Exon 5 of 12	NP_006490.3
	LGALS8	NM_201545.2		c.166A>C	p.Met56Leu	missense	Exon 5 of 12	NP_963839.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	ENST00000366584.9	TSL:1 MANE Select	c.166A>C	p.Met56Leu	missense	Exon 4 of 10	ENSP00000355543.4
	LGALS8	ENST00000450372.6	TSL:1	c.166A>C	p.Met56Leu	missense	Exon 5 of 12	ENSP00000408657.2
	LGALS8	ENST00000341872.10	TSL:1	c.166A>C	p.Met56Leu	missense	Exon 5 of 11	ENSP00000342139.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.77
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.52	N
PhyloP100		-0.12
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.028
Sift	Benign	0.96	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.070
MutPred		0.42		Loss of disorder (P = 0.1253)
MVP		0.32
MPC		0.051
ClinPred		0.098	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.18
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: rs1041937; hg19: chr1-236702210;