10-29292013-C-T

Variant names:

• chr10-29292013-C-T
• rs2209788
• NM_032517.6:c.139+7C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_032517.6(LYZL1):​c.139+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,096,142 control chromosomes in the GnomAD database, including 60,598 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (4783 hom., cov: 19)
  • Exomes 𝑓: 0.16 (55815 hom.)
• Consequence: LYZL1 NM_032517.6 splice_region, intron
• Scores: Splicing: ADA: 0.0001034
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.191
• Publications: 2 publications found

Genes affected

LYZL1 (HGNC:30502): (lysozyme like 1) Predicted to enable lysozyme activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000305098 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-29292013-C-T is Benign according to our data. Variant chr10-29292013-C-T is described in ClinVar as Benign. ClinVar VariationId is 769366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4783 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032517.6. 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
	LYZL1	NM_032517.6	MANE Select	c.139+7C>T		splice_region intron	N/A	NP_115906.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYZL1	ENST00000649382.2	MANE Select	c.139+7C>T		splice_region intron	N/A	ENSP00000498092.1	Q6UWQ5-1
	LYZL1	ENST00000375500.8	TSL:1	c.277+7C>T		splice_region intron	N/A	ENSP00000364650.3	Q6UWQ5-2
	LYZL1	ENST00000494304.1	TSL:3	n.82+7C>T		splice_region intron	N/A	ENSP00000434629.1	H0YDZ2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 24725 AN: 87722 Hom.: 4784 Cov.: 19

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.356

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.298

GnomAD2 exomes AF: 0.0451 AC: 7585 AN: 168146 AF XY: 0.0433

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.0533

Gnomad ASJ exome AF: 0.0315

Gnomad EAS exome AF: 0.126

Gnomad FIN exome AF: 0.0247

Gnomad NFE exome AF: 0.0423

Gnomad OTH exome AF: 0.0655

GnomAD4 exome AF: 0.165 AC: 165885 AN: 1008370 Hom.: 55815 Cov.: 33 AF XY: 0.170 AC XY: 85468 AN XY: 502094

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0922 AC: 2533 AN: 27482

American (AMR) AF: 0.223 AC: 6988 AN: 31400

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 5140 AN: 17686

East Asian (EAS) AF: 0.430 AC: 13393 AN: 31112

South Asian (SAS) AF: 0.199 AC: 12440 AN: 62490

European-Finnish (FIN) AF: 0.298 AC: 11524 AN: 38644

Middle Eastern (MID) AF: 0.178 AC: 685 AN: 3840

European-Non Finnish (NFE) AF: 0.138 AC: 103722 AN: 753066

Other (OTH) AF: 0.222 AC: 9460 AN: 42650

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.282 AC: 24725 AN: 87772 Hom.: 4783 Cov.: 19 AF XY: 0.268 AC XY: 11320 AN XY: 42188

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.164 AC: 4557 AN: 27712

American (AMR) AF: 0.314 AC: 2629 AN: 8362

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 685 AN: 1960

East Asian (EAS) AF: 0.368 AC: 1173 AN: 3186

South Asian (SAS) AF: 0.259 AC: 751 AN: 2898

European-Finnish (FIN) AF: 0.300 AC: 1664 AN: 5554

Middle Eastern (MID) AF: 0.360 AC: 67 AN: 186

European-Non Finnish (NFE) AF: 0.351 AC: 12702 AN: 36176

Other (OTH) AF: 0.297 AC: 356 AN: 1198

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.446 Hom.: 2283

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.1
DANN	Benign	0.50
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.092
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: rs2209788; hg19: chr10-29580942; COSMIC: COSV64966458;