14-60509250-C-T

Position:

chr14-60509250-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_007374.3(SIX6):c.-149C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 702,634 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 9 hom. )

Consequence

SIX6
NM_007374.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.236

Variant links:

Genes affected

SIX6 (HGNC:10892): (SIX homeobox 6) 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 eye development. Defects in this gene are a cause of isolated microphthalmia with cataract type 2 (MCOPCT2). [provided by RefSeq, Jul 2008]

SIX6 links:

C14orf39 (HGNC:19849): (chromosome 14 open reading frame 39) Predicted to be involved in gamete generation and meiosis I. Predicted to be located in chromosome. Predicted to be active in central element. Implicated in primary ovarian insufficiency 18 and spermatogenic failure 52. [provided by Alliance of Genome Resources, Apr 2022]

C14orf39 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 14-60509250-C-T is Benign according to our data. Variant chr14-60509250-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 313427.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00111 (169/152258) while in subpopulation EAS AF= 0.0189 (97/5142). AF 95% confidence interval is 0.0158. There are 2 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 169 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIX6	NM_007374.3 linkuse as main transcript	c.-149C>T		5_prime_UTR_variant	1/2	ENST00000327720.6
C14orf39	XM_047431324.1 linkuse as main transcript	c.-144+6145G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIX6	ENST00000327720.6 linkuse as main transcript	c.-149C>T		5_prime_UTR_variant	1/2	1	NM_007374.3	P1
C14orf39	ENST00000556799.1 linkuse as main transcript	c.-144+6145G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00111

AC:

169

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0188

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.00146

AC:

806

AN:

550376

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

392

AN XY:

291018

show subpopulations

Gnomad4 AFR exome

AF:

0.0000654

Gnomad4 AMR exome

AF:

0.00598

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0178

Gnomad4 SAS exome

AF:

0.000401

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000529

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00111

AC:

169

AN:

152258

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00385

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0189

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Bravo

AF:

0.00187

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Anophthalmia-microphthalmia syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.6

DANN

Benign

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over