22-37679636-G-T

Variant names:

• chr22-37679636-G-T
• rs375290542
• NM_002305.4:c.295G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002305.4(LGALS1):​c.295G>T​(p.Val99Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,722 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V99I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LGALS1 NM_002305.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463
• Publications: 1 publications found

Genes affected

LGALS1 (HGNC:6561): (galectin 1) The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. This gene product may act as an autocrine negative growth factor that regulates cell proliferation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002305.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS1	NM_002305.4	MANE Select	c.295G>T	p.Val99Phe	missense	Exon 4 of 4	NP_002296.1	P09382

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS1	ENST00000215909.10	TSL:1 MANE Select	c.295G>T	p.Val99Phe	missense	Exon 4 of 4	ENSP00000215909.5	P09382
	LGALS1	ENST00000895126.1		c.301G>T	p.Val101Phe	missense	Exon 4 of 4	ENSP00000565185.1
	LGALS1	ENST00000895125.1		c.274G>T	p.Val92Phe	missense	Exon 4 of 4	ENSP00000565184.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246316 AF XY: 0.00000750

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456722 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724524

African (AFR) AF: 0.00 AC: 0 AN: 33332

American (AMR) AF: 0.00 AC: 0 AN: 43864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39302

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 85062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110192

Other (OTH) AF: 0.00 AC: 0 AN: 60190

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		0.46
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.96	D
Vest4		0.70
MutPred		0.70		Loss of ubiquitination at K100 (P = 0.1668)
MVP		0.23
MPC		0.98
ClinPred		0.96	D
GERP RS		-0.047
Varity_R		0.90
gMVP		0.97
Mutation Taster		=54/46	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: rs375290542; hg19: chr22-38075643;