5-10249898-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000509915.1(ENSG00000248968):n.671A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 818,222 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (29 hom., cov: 0)
  • Exomes 𝑓: 0.012 (139 hom.)
• Consequence: ENST00000509915.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.677

Genes affected

(HGNC:):

ATPSCKMT (HGNC:27029): (ATP synthase c subunit lysine N-methyltransferase) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine trimethylation; positive regulation of sensory perception of pain; and regulation of proton transport. Located in mitochondrial crista. [provided by Alliance of Genome Resources, Apr 2022]

CCT5 (HGNC:1618): (chaperonin containing TCP1 subunit 5) The protein encoded by this gene is a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Mutations in this gene cause hereditary sensory and autonomic neuropathy with spastic paraplegia (HSNSP). Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 5 and 13. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-10249898-A-T is Benign according to our data. Variant chr5-10249898-A-T is described in ClinVar as [Benign]. Clinvar id is 1272001.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATPSCKMT	NM_199133.4			upstream_gene_variant		ENST00000511437.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000509915.1	n.671A>T		non_coding_transcript_exon_variant	2/2	3
ATPSCKMT	ENST00000511437.6			upstream_gene_variant		1	NM_199133.4	P1

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 1481 AN: 21820 Hom.: 29 Cov.: 0

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0876

GnomAD3 exomes AF: 0.157 AC: 2627 AN: 16728 Hom.: 22 AF XY: 0.160 AC XY: 1403 AN XY: 8794

Gnomad AFR exome AF: 0.323

Gnomad AMR exome AF: 0.0832

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.144

Gnomad SAS exome AF: 0.137

Gnomad FIN exome AF: 0.0544

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.0116 AC: 9234 AN: 796404 Hom.: 139 Cov.: 50 AF XY: 0.0121 AC XY: 4690 AN XY: 387296

Gnomad4 AFR exome AF: 0.0614

Gnomad4 AMR exome AF: 0.0288

Gnomad4 ASJ exome AF: 0.0176

Gnomad4 EAS exome AF: 0.0108

Gnomad4 SAS exome AF: 0.0176

Gnomad4 FIN exome AF: 0.0316

Gnomad4 NFE exome AF: 0.00965

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome AF: 0.0679 AC: 1482 AN: 21818 Hom.: 29 Cov.: 0 AF XY: 0.0638 AC XY: 687 AN XY: 10774

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.0423

Gnomad4 EAS AF: 0.0526

Gnomad4 SAS AF: 0.0630

Gnomad4 FIN AF: 0.0145

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0882

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

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.74
Dann	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs754302392; hg19: chr5-10250010;