chr10-29292015-C-A

Variant names:

• chr10-29292015-C-A
• rs1774948
• NM_032517.6:c.139+9C>A

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+9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,101,922 control chromosomes in the GnomAD database, including 59,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (4769 hom., cov: 19)
  • Exomes 𝑓: 0.16 (54332 hom.)
• Consequence: LYZL1 NM_032517.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0280
• Publications: 3 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 10-29292015-C-A is Benign according to our data. Variant chr10-29292015-C-A is described in ClinVar as Benign. ClinVar VariationId is 769367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4769 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+9C>A		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+9C>A		intron	N/A	ENSP00000498092.1	Q6UWQ5-1
	LYZL1	ENST00000375500.8	TSL:1	c.277+9C>A		intron	N/A	ENSP00000364650.3	Q6UWQ5-2
	LYZL1	ENST00000494304.1	TSL:3	n.82+9C>A		intron	N/A	ENSP00000434629.1	H0YDZ2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 24585 AN: 87924 Hom.: 4770 Cov.: 19

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.301

GnomAD2 exomes AF: 0.0402 AC: 6738 AN: 167764 AF XY: 0.0384

Gnomad AFR exome AF: 0.0198

Gnomad AMR exome AF: 0.0453

Gnomad ASJ exome AF: 0.0273

Gnomad EAS exome AF: 0.112

Gnomad FIN exome AF: 0.0239

Gnomad NFE exome AF: 0.0378

Gnomad OTH exome AF: 0.0571

GnomAD4 exome AF: 0.160 AC: 161809 AN: 1013952 Hom.: 54332 Cov.: 33 AF XY: 0.165 AC XY: 83253 AN XY: 504362

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

African (AFR) AF: 0.0900 AC: 2493 AN: 27710

American (AMR) AF: 0.218 AC: 6910 AN: 31666

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 5048 AN: 17758

East Asian (EAS) AF: 0.430 AC: 13332 AN: 31012

South Asian (SAS) AF: 0.194 AC: 12177 AN: 62748

European-Finnish (FIN) AF: 0.291 AC: 11132 AN: 38294

Middle Eastern (MID) AF: 0.176 AC: 684 AN: 3876

European-Non Finnish (NFE) AF: 0.133 AC: 100787 AN: 758102

Other (OTH) AF: 0.216 AC: 9246 AN: 42786

⚠️ 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: 0.279 AC: 24582 AN: 87970 Hom.: 4769 Cov.: 19 AF XY: 0.266 AC XY: 11252 AN XY: 42320

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

African (AFR) AF: 0.164 AC: 4552 AN: 27780

American (AMR) AF: 0.309 AC: 2578 AN: 8334

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 671 AN: 1950

East Asian (EAS) AF: 0.366 AC: 1166 AN: 3188

South Asian (SAS) AF: 0.258 AC: 749 AN: 2904

European-Finnish (FIN) AF: 0.294 AC: 1640 AN: 5570

Middle Eastern (MID) AF: 0.379 AC: 72 AN: 190

European-Non Finnish (NFE) AF: 0.349 AC: 12650 AN: 36278

Other (OTH) AF: 0.299 AC: 363 AN: 1214

⚠️ 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: 0.444 Hom.: 2271

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	7.5
DANN	Benign	0.62
PhyloP100		-0.028
Mutation Taster		=100/0	polymorphism (auto)

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: rs1774948; hg19: chr10-29580944; COSMIC: COSV64966946;