7-77010554-T-C

Variant names:

• chr7-77010554-T-C
• rs6955651
• ENST00000579700.2:n.815+4779T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000579700.2(DTX2P1-UPK3BP1-PMS2P11):​n.815+4779T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.83 (46664 hom., cov: 16)
• Consequence: DTX2P1-UPK3BP1-PMS2P11 ENST00000579700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 12 publications found

Genes affected

DTX2P1-UPK3BP1-PMS2P11 (HGNC:42360): (DTX2P1-UPK3BP1-PMS2P11 readthrough, transcribed pseudogene) This locus represents naturally-occurring readthrough transcription spanning multiple pseudogenes: DTX2P1 (DTX2 pseudogene 1), UPK3BP1 (uroplakin 3B pseudogene 1), PMS2P11 (PMS1 homolog 2, mismatch repair system component pseudogene 11). Some transcripts may also extend to PMS2P9 (PMS1 homolog 2, mismatch repair system component pseudogene 9). The readthrough transcripts likely do not encode functional proteins. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BS2: High Homozygotes in GnomAd4 at 46664 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTX2P1-UPK3BP1-PMS2P11	NR_023383.1	n.1096-1326T>C		intron_variant	Intron 6 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTX2P1-UPK3BP1-PMS2P11	ENST00000579700.2	n.815+4779T>C		intron_variant	Intron 6 of 10	2
DTX2P1-UPK3BP1-PMS2P11	ENST00000584900.5	n.969-1326T>C		intron_variant	Intron 6 of 10	2
DTX2P1-UPK3BP1-PMS2P11	ENST00000636308.1	n.2007-1326T>C		intron_variant	Intron 10 of 14	5

Frequencies

GnomAD3 genomes AF: 0.831 AC: 110031 AN: 132458 Hom.: 46614 Cov.: 16

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.773

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.801

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.831 AC: 110123 AN: 132556 Hom.: 46664 Cov.: 16 AF XY: 0.818 AC XY: 51883 AN XY: 63450

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

African (AFR) AF: 0.958 AC: 33327 AN: 34798

American (AMR) AF: 0.678 AC: 8925 AN: 13158

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 2537 AN: 3266

East Asian (EAS) AF: 0.602 AC: 2876 AN: 4778

South Asian (SAS) AF: 0.630 AC: 2450 AN: 3890

European-Finnish (FIN) AF: 0.774 AC: 6227 AN: 8048

Middle Eastern (MID) AF: 0.784 AC: 221 AN: 282

European-Non Finnish (NFE) AF: 0.832 AC: 51412 AN: 61770

Other (OTH) AF: 0.802 AC: 1386 AN: 1728

⚠️ 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: 0.844 Hom.: 20937

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.90
DANN	Benign	0.50
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs6955651; hg19: chr7-76639871; COSMIC: COSV50831096;