14-60645516-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005982.4(SIX1):c.*766del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.79 (46469 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: SIX1 NM_005982.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.213

Genes affected

SIX1 (HGNC:10887): (SIX homeobox 1) The protein encoded by this gene is a homeobox protein that is similar to the Drosophila 'sine oculis' gene product. This gene is found in a cluster of related genes on chromosome 14 and is thought to be involved in limb development. Defects in this gene are a cause of autosomal dominant deafness type 23 (DFNA23) and branchiootic syndrome type 3 (BOS3). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-60645516-TA-T is Benign according to our data. Variant chr14-60645516-TA-T is described in ClinVar as [Benign]. Clinvar id is 313450.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIX1	NM_005982.4	c.*766del		3_prime_UTR_variant	2/2	ENST00000645694.3
SIX1	XM_017021602.3	c.*1040del		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIX1	ENST00000645694.3	c.*766del		3_prime_UTR_variant	2/2		NM_005982.4	P1
SIX1	ENST00000554986.2	c.*766del		3_prime_UTR_variant	2/2	3
SIX1	ENST00000553535.2	n.1309del		non_coding_transcript_exon_variant	3/3	3
SIX1	ENST00000555955.3	n.2258del		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.789 AC: 116458 AN: 147674 Hom.: 46460 Cov.: 0

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.785

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.789 AC: 116481 AN: 147722 Hom.: 46469 Cov.: 0 AF XY: 0.790 AC XY: 56815 AN XY: 71878

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.912

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.785

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Nonsyndromic Hearing Loss, Dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Branchiootorenal Spectrum Disorders Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs33943216; hg19: chr14-61112234;