16-23445969-TAAAAAA-TAAA

Variant names:

• chr16-23445969-TAAA-T
• rs71379679
• NM_153603.4:c.170-11_170-9delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_153603.4(COG7):​c.170-11_170-9delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,471,896 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0029 (0 hom.)
• Consequence: COG7 NM_153603.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.874
• 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), PanelApp Australia, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Variant has high frequency in the AMR (0.0053) population. However there is too low homozygotes in high coverage region: (expected more than 2, got 0).
• BP6: Variant 16-23445969-TAAA-T is Benign according to our data. Variant chr16-23445969-TAAA-T is described in ClinVar as Benign. ClinVar VariationId is 235231.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG7	NM_153603.4	c.170-11_170-9delTTT		intron_variant	Intron 1 of 16	ENST00000307149.10	NP_705831.1
COG7	XM_017023870.2	c.-26-11_-26-9delTTT		intron_variant	Intron 1 of 16		XP_016879359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG7	ENST00000307149.10	c.170-11_170-9delTTT		intron_variant	Intron 1 of 16	1	NM_153603.4	ENSP00000305442.5

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 15 AN: 129204 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000562

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000117

Gnomad OTH AF: 0.000575

GnomAD2 exomes AF: 0.00704 AC: 1073 AN: 152462 AF XY: 0.00730

Gnomad AFR exome AF: 0.00543

Gnomad AMR exome AF: 0.00752

Gnomad ASJ exome AF: 0.00352

Gnomad EAS exome AF: 0.00775

Gnomad FIN exome AF: 0.00792

Gnomad NFE exome AF: 0.00730

Gnomad OTH exome AF: 0.00338

GnomAD4 exome AF: 0.00295 AC: 3955 AN: 1342692 Hom.: 0 AF XY: 0.00291 AC XY: 1945 AN XY: 669258

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

African (AFR) AF: 0.00400 AC: 118 AN: 29526

American (AMR) AF: 0.00594 AC: 226 AN: 38068

Ashkenazi Jewish (ASJ) AF: 0.00264 AC: 64 AN: 24238

East Asian (EAS) AF: 0.00476 AC: 176 AN: 36996

South Asian (SAS) AF: 0.00313 AC: 246 AN: 78542

European-Finnish (FIN) AF: 0.00562 AC: 229 AN: 40768

Middle Eastern (MID) AF: 0.00279 AC: 14 AN: 5020

European-Non Finnish (NFE) AF: 0.00259 AC: 2674 AN: 1033720

Other (OTH) AF: 0.00373 AC: 208 AN: 55814

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000116 AC: 15 AN: 129204 Hom.: 0 Cov.: 25 AF XY: 0.000177 AC XY: 11 AN XY: 62150

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

African (AFR) AF: 0.0000286 AC: 1 AN: 34986

American (AMR) AF: 0.000159 AC: 2 AN: 12614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3108

East Asian (EAS) AF: 0.00 AC: 0 AN: 4590

South Asian (SAS) AF: 0.00 AC: 0 AN: 4122

European-Finnish (FIN) AF: 0.000562 AC: 4 AN: 7116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.000117 AC: 7 AN: 59848

Other (OTH) AF: 0.000575 AC: 1 AN: 1738

⚠️ 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: 0.00269 Hom.: 4

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 29, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.87
Mutation Taster		=100/0	polymorphism

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: rs71379679; hg19: chr16-23457290;