ENST00000677024.1:n.-206A>C

Variant names:

• chr19-45692197-G-C
• NM_004597.6:c.-136C>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.-507G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: QPCTL ENST00000677024.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• Publications: 0 publications found

Genes affected

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]

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]

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=-0.95).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000677024.1. 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
	SNRPD2	NM_004597.6		c.-136C>G		5_prime_UTR	Exon 1 of 4	NP_004588.1	P62316-1
	SNRPD2	NM_001384647.1	MANE Select	c.-309C>G		upstream_gene	N/A	NP_001371576.1	P62316-1
	SNRPD2	NM_001369751.1		c.-435C>G		upstream_gene	N/A	NP_001356680.1	P62316-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPD2	ENST00000588301.5	TSL:3	c.-136C>G		5_prime_UTR	Exon 1 of 4	ENSP00000465216.1	P62316-1
	SNRPD2	ENST00000587579.1	TSL:5	n.247C>G		non_coding_transcript_exon	Exon 2 of 2
	SNRPD2	ENST00000342669.8	TSL:1 MANE Select	c.-309C>G		upstream_gene	N/A	ENSP00000342374.2	P62316-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 6

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.5
DANN	Benign	0.73
PhyloP100		-0.16
PromoterAI		0.29	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

hg19: chr19-46195455;