1-236537507-T-C

Variant names:

• chr1-236537507-T-C
• rs1126407
• NM_201544.4:c.56T>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_201544.4(LGALS8):​c.56T>C​(p.Phe19Ser) 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 pathogenic 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: 2.11
• Publications: 42 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.953

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.56T>C	p.Phe19Ser	missense	Exon 3 of 10	NP_963838.1
	LGALS8	NM_006499.5		c.56T>C	p.Phe19Ser	missense	Exon 4 of 12	NP_006490.3
	LGALS8	NM_201545.2		c.56T>C	p.Phe19Ser	missense	Exon 4 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.56T>C	p.Phe19Ser	missense	Exon 3 of 10	ENSP00000355543.4
	LGALS8	ENST00000450372.6	TSL:1	c.56T>C	p.Phe19Ser	missense	Exon 4 of 12	ENSP00000408657.2
	LGALS8	ENST00000341872.10	TSL:1	c.56T>C	p.Phe19Ser	missense	Exon 4 of 11	ENSP00000342139.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		2.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.95	P
Vest4		0.42
MutPred		0.90		Gain of disorder (P = 0.0466)
MVP		0.50
MPC		0.31
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.89
gMVP		0.94
Mutation Taster		=61/39	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: rs1126407; hg19: chr1-236700807;