chr16-25161210-AT-A

Position:

• chr16-25161210-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_016309.3(LCMT1):​c.569+17del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,274,348 control chromosomes in the GnomAD database, including 13 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (8 hom., cov: 32)
  • Exomes 𝑓: 0.017 (5 hom.)
• Consequence: LCMT1 NM_016309.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.149

Genes affected

LCMT1 (HGNC:17557): (leucine carboxyl methyltransferase 1) LCMT1 catalyzes the methylation of the carboxyl group of the C-terminal leucine residue (leu309) of the catalytic subunit of protein phosphatase-2A (PPP2CA; MIM 176915) (De Baere et al., 1999 [PubMed 10600115]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-25161210-AT-A is Benign according to our data. Variant chr16-25161210-AT-A is described in ClinVar as [Benign]. Clinvar id is 771916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0057 (849/148922) while in subpopulation AFR AF= 0.0181 (739/40772). AF 95% confidence interval is 0.017. There are 8 homozygotes in gnomad4. There are 410 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCMT1	NM_016309.3	c.569+17del		splice_region_variant, intron_variant		ENST00000399069.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCMT1	ENST00000399069.8	c.569+17del		splice_region_variant, intron_variant		1	NM_016309.3	P1

Frequencies

GnomAD3 genomes AF: 0.00568 AC: 846 AN: 148818 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00310

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.000203

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000672

Gnomad OTH AF: 0.00442

GnomAD4 exome AF: 0.0165 AC: 18617 AN: 1125426 Hom.: 5 Cov.: 19 AF XY: 0.0165 AC XY: 9161 AN XY: 554846

Gnomad4 AFR exome AF: 0.0380

Gnomad4 AMR exome AF: 0.0222

Gnomad4 ASJ exome AF: 0.0158

Gnomad4 EAS exome AF: 0.0146

Gnomad4 SAS exome AF: 0.0196

Gnomad4 FIN exome AF: 0.0155

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0180

GnomAD4 genome AF: 0.00570 AC: 849 AN: 148922 Hom.: 8 Cov.: 32 AF XY: 0.00565 AC XY: 410 AN XY: 72594

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.00310

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.000203

Gnomad4 NFE AF: 0.000672

Gnomad4 OTH AF: 0.00438

Alfa AF: 0.0325 Hom.: 0

Bravo AF: 0.00642

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs761843189; hg19: chr16-25172531;