19-38803888-G-T

Variant names:

• chr19-38803888-G-T
• rs767409129
• NM_006149.4:c.482C>A

Variant summary

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

The NM_006149.4(LGALS4):​c.482C>A​(p.Pro161Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P161L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LGALS4 NM_006149.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 1 publications found

Genes affected

LGALS4 (HGNC:6565): (galectin 4) The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. The expression of this gene is restricted to small intestine, colon, and rectum, and it is underexpressed in colorectal cancer. [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=0.042205036).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006149.4. 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
	LGALS4	NM_006149.4	MANE Select	c.482C>A	p.Pro161Gln	missense	Exon 5 of 10	NP_006140.1	Q6FHZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS4	ENST00000307751.9	TSL:1 MANE Select	c.482C>A	p.Pro161Gln	missense	Exon 5 of 10	ENSP00000302100.3	P56470
	LGALS4	ENST00000908464.1		c.362C>A	p.Pro121Gln	missense	Exon 5 of 10	ENSP00000578523.1
	LGALS4	ENST00000908463.1		c.347C>A	p.Pro116Gln	missense	Exon 4 of 9	ENSP00000578522.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241638 AF XY: 0.00000766

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: 6.86e-7 AC: 1 AN: 1457082 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724412

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.00 AC: 0 AN: 43976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109720

Other (OTH) AF: 0.00 AC: 0 AN: 60198

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.78
DANN	Benign	0.16
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.077
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.021
Sift	Benign	0.63	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.17		Loss of glycosylation at P161 (P = 0.0124)
MVP		0.088
MPC		0.098
ClinPred		0.024	T
GERP RS		1.6
Varity_R		0.031
gMVP		0.18
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs767409129; hg19: chr19-39294528;