19-13099394-G-T

Position:

• chr19-13099394-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000264824.5(LYL1):​c.768C>A​(p.Asp256Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: LYL1 ENST00000264824.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

Genes affected

LYL1 (HGNC:6734): (LYL1 basic helix-loop-helix family member) This gene represents a basic helix-loop-helix transcription factor. The encoded protein may play roles in blood vessel maturation and hematopoeisis. A translocation between this locus and the T cell receptor beta locus (GeneID 6957) on chromosome 7 has been associated with acute lymphoblastic leukemia. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19267535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYL1	NM_005583.5	c.768C>A	p.Asp256Glu	missense_variant	4/4	ENST00000264824.5	NP_005574.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYL1	ENST00000264824.5	c.768C>A	p.Asp256Glu	missense_variant	4/4	1	NM_005583.5	ENSP00000264824.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096746 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 519054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jun 29, 2023

The c.768C>A (p.D256E) alteration is located in exon 4 (coding exon 3) of the LYL1 gene. This alteration results from a C to A substitution at nucleotide position 768, causing the aspartic acid (D) at amino acid position 256 to be replaced by a glutamic acid (E). 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	0.10
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.92
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.35	T
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	0.078	D
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.89	N
REVEL	Uncertain	0.32
Sift	Benign	0.044	D
Sift4G	Benign	0.51	T
Polyphen		0.039	B
Vest4		0.051
MutPred		0.26		Gain of relative solvent accessibility (P = 0.1012);
MVP		0.44
MPC		1.2
ClinPred		0.12	T
GERP RS		-1.1
Varity_R		0.036
gMVP		0.26

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: chr19-13210208;