16-75694133-T-C

Position:

• chr16-75694133-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001351307.2(DUXB):​c.834A>G​(p.Gln278Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 430,766 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (3 hom.)
• Consequence: DUXB NM_001351307.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.245

Genes affected

DUXB (HGNC:33345): (double homeobox B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TERF2IP (HGNC:19246): (TERF2 interacting protein) Enables G-rich strand telomeric DNA binding activity and phosphatase binding activity. Involved in several processes, including positive regulation of NIK/NF-kappaB signaling; regulation of nucleobase-containing compound metabolic process; and regulation of protein modification process. Located in chromosome, telomeric region; cytosol; and nuclear body. Part of shelterin complex. [provided by Alliance of Genome Resources, Apr 2022]

TERF2IP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-75694133-T-C is Benign according to our data. Variant chr16-75694133-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3341656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.245 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUXB	NM_001351307.2	c.834A>G	p.Gln278Gln	synonymous_variant	5/5	ENST00000633875.4	NP_001338236.1
DUXB	NM_001351308.2	c.573A>G	p.Gln191Gln	synonymous_variant	3/3		NP_001338237.1
DUXB	NM_001351309.2	c.393A>G	p.Gln131Gln	synonymous_variant	4/4		NP_001338238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUXB	ENST00000633875.4	c.834A>G	p.Gln278Gln	synonymous_variant	5/5	3	NM_001351307.2	ENSP00000491301.1
TERF2IP	ENST00000653858.1	c.795+39736T>C		intron_variant				ENSP00000499565.1
TERF2IP	ENST00000564671.2	c.135+37792T>C		intron_variant		2		ENSP00000456092.1
TERF2IP	ENST00000659145.1	n.110+37792T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 386 AN: 152188 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00257

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00314 AC: 875 AN: 278460 Hom.: 3 Cov.: 0 AF XY: 0.00308 AC XY: 438 AN XY: 142040

Gnomad4 AFR exome AF: 0.000257

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.000202

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0137

Gnomad4 NFE exome AF: 0.00288

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.00253 AC: 386 AN: 152306 Hom.: 3 Cov.: 32 AF XY: 0.00290 AC XY: 216 AN XY: 74476

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0159

Gnomad4 NFE AF: 0.00257

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00302 Hom.: 1

Bravo AF: 0.00143

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

DUXB: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs138025701; hg19: chr16-75728031;