chr17-20456575-A-G

Position:

• chr17-20456575-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001367292.2(LGALS9B):​c.430T>C​(p.Tyr144His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 2)
• Consequence: LGALS9B NM_001367292.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.488

Genes affected

LGALS9B (HGNC:24842): (galectin 9B) This gene was initially thought to represent a pseudogene of galectin 9; however, this transcript has good exon-intron structure and encodes a predicted protein of the same size as and highly similar to galectin 9. This gene is one of two similar loci on chromosome 17p similar to galectin 9 and now thought to be protein-encoding. This gene is the more centromeric gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11205429).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9B	NM_001367292.2	c.430T>C	p.Tyr144His	missense_variant	4/11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3	c.430T>C	p.Tyr144His	missense_variant	4/11		NP_001036150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS9B	ENST00000423676.8	c.430T>C	p.Tyr144His	missense_variant	4/11	1	NM_001367292.2	ENSP00000388841.3

Frequencies

GnomAD3 genomes Cov.: 2

GnomAD4 exome Cov.: 6

GnomAD4 genome Cov.: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2021

The c.430T>C (p.Y144H) alteration is located in exon 4 (coding exon 4) of the LGALS9B gene. This alteration results from a T to C substitution at nucleotide position 430, causing the tyrosine (Y) at amino acid position 144 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.69
DEOGEN2	Benign	0.0055	T;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.024
Sift	Benign	0.55	T;T
Sift4G	Benign	0.51	T;T
Polyphen		0.0030	B;B
Vest4		0.24
MutPred		0.57		Gain of disorder (P = 0.0255);Gain of disorder (P = 0.0255);
MVP		0.014
ClinPred		0.073	T
GERP RS		0.58
Varity_R		0.098
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-20359888;