17-8173297-GAACA-G

Position:

• chr17-8173297-GAACA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000437139.7(TMEM107):​c.*902_*905del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 533,686 control chromosomes in the GnomAD database, including 75 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (57 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (18 hom.)
• Consequence: TMEM107 ENST00000437139.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.899

Genes affected

TMEM107 (HGNC:28128): (transmembrane protein 107) This gene encodes a transmembrane protein and component of the primary cilia transition zone. The encoded protein regulates ciliogenesis and ciliary protein composition. Human fibroblasts expressing a mutant allele of this gene exhibit reduced numbers of cilia, altered cilia length, and impaired sonic hedgehog signaling. In human patients, different mutations in this gene cause different ciliopathies, including Meckel-Gruber syndrome and orofaciodigital syndrome. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-8173297-GAACA-G is Benign according to our data. Variant chr17-8173297-GAACA-G is described in ClinVar as [Benign]. Clinvar id is 1278253.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0145 (2212/152206) while in subpopulation AFR AF= 0.0504 (2091/41528). AF 95% confidence interval is 0.0486. There are 57 homozygotes in gnomad4. There are 1048 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM107	NM_183065.4	c.*902_*905del		3_prime_UTR_variant	5/5	ENST00000437139.7	NP_898888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM107	ENST00000437139.7	c.*902_*905del		3_prime_UTR_variant	5/5	1	NM_183065.4	ENSP00000402732	P1
TMEM107	ENST00000449985.6	c.*951_*954del		3_prime_UTR_variant	2/2	1		ENSP00000404753

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2206 AN: 152088 Hom.: 55 Cov.: 31

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00184 AC: 703 AN: 381480 Hom.: 18 AF XY: 0.00151 AC XY: 305 AN XY: 202236

Gnomad4 AFR exome AF: 0.0461

Gnomad4 AMR exome AF: 0.00252

Gnomad4 ASJ exome AF: 0.0000845

Gnomad4 EAS exome AF: 0.000134

Gnomad4 SAS exome AF: 0.000488

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000296

Gnomad4 OTH exome AF: 0.00296

GnomAD4 genome AF: 0.0145 AC: 2212 AN: 152206 Hom.: 57 Cov.: 31 AF XY: 0.0141 AC XY: 1048 AN XY: 74434

Gnomad4 AFR AF: 0.0504

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0120 Hom.: 0

Bravo AF: 0.0163

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 31, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs150834230; hg19: chr17-8076615;