1-236537507-T-C

Position:

• chr1-236537507-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F19Y) 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: 2.11

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_pathogenic. Variant got 6 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS8	NM_201544.4	c.56T>C	p.Phe19Ser	missense_variant	3/10	ENST00000366584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS8	ENST00000366584.9	c.56T>C	p.Phe19Ser	missense_variant	3/10	1	NM_201544.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;.;.;T;T;.;T;.;T;T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.83	T;T;.;D;.;T;.;T;.;T;T;.;D;T;T;.
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	2.9	.;.;M;.;M;.;M;.;M;.;M;M;.;.;M;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.7	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.95, 0.98, 0.91	.;.;P;.;P;.;P;.;D;P;P;D;.;.;D;P
Vest4		0.42, 0.41, 0.36, 0.44, 0.41, 0.35, 0.44, 0.35, 0.40
MutPred		0.90		Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);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

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: rs1126407; hg19: chr1-236700807;