19-45692498-A-G

Variant names:

• chr19-45692498-A-G
• rs7245708
• ENST00000677024.1:n.-206A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000677024.1(QPCTL):​n.-206A>G 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 0.00000321 in 311,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: QPCTL ENST00000677024.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934
• Publications: 0 publications found

Genes affected

QPCTL (HGNC:25952): (glutaminyl-peptide cyclotransferase like) Enables glutaminyl-peptide cyclotransferase activity and zinc ion binding activity. Acts upstream of or within peptidyl-pyroglutamic acid biosynthetic process, using glutaminyl-peptide cyclotransferase. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

SNRPD2 (HGNC:11159): (small nuclear ribonucleoprotein D2 polypeptide) The protein encoded by this gene belongs to the small nuclear ribonucleoprotein core protein family. It is required for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QPCTL	NM_017659.4	c.-206A>G		upstream_gene_variant		ENST00000012049.10	NP_060129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QPCTL	ENST00000012049.10	c.-206A>G		upstream_gene_variant		2	NM_017659.4	ENSP00000012049.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000321 AC: 1 AN: 311494 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 160124

African (AFR) AF: 0.00 AC: 0 AN: 8988

American (AMR) AF: 0.00 AC: 0 AN: 10766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10114

East Asian (EAS) AF: 0.00 AC: 0 AN: 24922

South Asian (SAS) AF: 0.00 AC: 0 AN: 14260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1470

European-Non Finnish (NFE) AF: 0.00000501 AC: 1 AN: 199656

Other (OTH) AF: 0.00 AC: 0 AN: 18906

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.69
PhyloP100		-0.93
PromoterAI		-0.00060	Neutral

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

Other links and lift over

dbSNP: rs7245708; hg19: chr19-46195756;