17-73208144-C-T

Position:

• chr17-73208144-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001098832.2(FAM104A):​c.*1385G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 1,508,214 control chromosomes in the GnomAD database, including 5,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (411 hom., cov: 32)
  • Exomes 𝑓: 0.083 (5079 hom.)
• Consequence: FAM104A NM_001098832.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00200

Genes affected

FAM104A (HGNC:25918): (VCP nuclear cofactor family member 1)

COG1 (HGNC:6545): (component of oligomeric golgi complex 1) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. It is thought that this protein is required for steps in the normal medial and trans Golgi-associated processing of glycoconjugates and plays a role in the organization of the Golgi-localized complex. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-73208144-C-T is Benign according to our data. Variant chr17-73208144-C-T is described in ClinVar as [Benign]. Clinvar id is 1183906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.084 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM104A	NM_001098832.2	c.*1385G>A		3_prime_UTR_variant	4/4	ENST00000405159.8
COG1	NM_018714.3	c.2806-170C>T		intron_variant		ENST00000299886.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM104A	ENST00000405159.8	c.*1385G>A		3_prime_UTR_variant	4/4	1	NM_001098832.2
COG1	ENST00000299886.9	c.2806-170C>T		intron_variant		1	NM_018714.3	P1

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 10062 AN: 152194 Hom.: 414 Cov.: 32

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.0831 AC: 112660 AN: 1355902 Hom.: 5079 Cov.: 33 AF XY: 0.0827 AC XY: 55047 AN XY: 665802

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.0540

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.000395

Gnomad4 SAS exome AF: 0.0674

Gnomad4 FIN exome AF: 0.0655

Gnomad4 NFE exome AF: 0.0892

Gnomad4 OTH exome AF: 0.0815

GnomAD4 genome AF: 0.0660 AC: 10058 AN: 152312 Hom.: 411 Cov.: 32 AF XY: 0.0645 AC XY: 4806 AN XY: 74480

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.0769

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0671

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.0737

Alfa AF: 0.0685 Hom.: 57

Bravo AF: 0.0658

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs76058650; hg19: chr17-71204283;