16-23445969-TAAAAAA-T

Variant names:

• chr16-23445969-TAAAAAA-T
• rs71379679
• NM_153603.4:c.170-14_170-9delTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153603.4(COG7):​c.170-14_170-9delTTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.0000022 in 1,362,972 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: COG7 NM_153603.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 2 publications found

Genes affected

COG7 (HGNC:18622): (component of oligomeric golgi complex 7) The protein encoded by this gene resides in the golgi, and constitutes one of the 8 subunits of the conserved oligomeric Golgi (COG) complex, which is required for normal golgi morphology and localization. Mutations in this gene are associated with the congenital disorder of glycosylation type IIe.[provided by RefSeq, May 2010]

COG7 Gene-Disease associations (from GenCC):

• COG7-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153603.4. 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
	COG7	NM_153603.4	MANE Select	c.170-14_170-9delTTTTTT		intron	N/A	NP_705831.1	A0A0S2Z652

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG7	ENST00000307149.10	TSL:1 MANE Select	c.170-14_170-9delTTTTTT		intron	N/A	ENSP00000305442.5	P83436
	COG7	ENST00000941095.1		c.170-14_170-9delTTTTTT		intron	N/A	ENSP00000611154.1
	COG7	ENST00000916651.1		c.170-14_170-9delTTTTTT		intron	N/A	ENSP00000586710.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000220 AC: 3 AN: 1362972 Hom.: 0 AF XY: 0.00000295 AC XY: 2 AN XY: 678998

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

African (AFR) AF: 0.00 AC: 0 AN: 29976

American (AMR) AF: 0.0000519 AC: 2 AN: 38562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24648

East Asian (EAS) AF: 0.00 AC: 0 AN: 37726

South Asian (SAS) AF: 0.00 AC: 0 AN: 79316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5094

European-Non Finnish (NFE) AF: 9.53e-7 AC: 1 AN: 1049488

Other (OTH) AF: 0.00 AC: 0 AN: 56648

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0953088), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

Splicing

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

Other links and lift over

dbSNP: rs71379679; hg19: chr16-23457290;