rs1041937

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-236538910-A-C
• chr1-236538910-A-G

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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. M56V) has been classified as Likely benign.

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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS8	NM_201544.4	c.166A>C	p.Met56Leu	missense_variant	Exon 4 of 10	ENST00000366584.9	NP_963838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS8	ENST00000366584.9	c.166A>C	p.Met56Leu	missense_variant	Exon 4 of 10	1	NM_201544.4	ENSP00000355543.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;.;T;T;.;T;.;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.23	T;T;.;T;.;T;.;.;T;T;.;T;T;.
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.022	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.52	.;.;N;.;N;.;N;N;.;N;N;.;N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.050	N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.028
Sift	Benign	0.96	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.41	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	.;.;B;.;B;.;B;B;B;B;B;.;B;B
Vest4		0.070, 0.095, 0.069, 0.080, 0.10, 0.072, 0.083, 0.090
MutPred		0.42		Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);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

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: rs1041937; hg19: chr1-236702210;