chr19-45765340-G-C

Position:

• chr19-45765340-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_175875.5(SIX5):​c.*161C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 994,828 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (14 hom.)
• Consequence: SIX5 NM_175875.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.658

Genes affected

SIX5 (HGNC:10891): (SIX homeobox 5) The protein encoded by this gene is a homeodomain-containing transcription factor that appears to function in the regulation of organogenesis. This gene is located downstream of the dystrophia myotonica-protein kinase gene. Mutations in this gene are a cause of branchiootorenal syndrome type 2. [provided by RefSeq, Jul 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-45765340-G-C is Benign according to our data. Variant chr19-45765340-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1318318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 547 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIX5	NM_175875.5	c.*161C>G		3_prime_UTR_variant	3/3	ENST00000317578.7	NP_787071.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIX5	ENST00000317578.7	c.*161C>G		3_prime_UTR_variant	3/3	1	NM_175875.5	ENSP00000316842	P1
	ENST00000559756.1	n.556G>C		non_coding_transcript_exon_variant	1/2	3
SIX5	ENST00000560160.1	c.*591C>G		3_prime_UTR_variant	2/2	2		ENSP00000453239

Frequencies

GnomAD3 genomes AF: 0.00359 AC: 547 AN: 152182 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00534

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00324 AC: 2727 AN: 842528 Hom.: 14 Cov.: 12 AF XY: 0.00316 AC XY: 1390 AN XY: 440132

Gnomad4 AFR exome AF: 0.000550

Gnomad4 AMR exome AF: 0.000141

Gnomad4 ASJ exome AF: 0.00634

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000284

Gnomad4 FIN exome AF: 0.0160

Gnomad4 NFE exome AF: 0.00327

Gnomad4 OTH exome AF: 0.00274

GnomAD4 genome AF: 0.00359 AC: 547 AN: 152300 Hom.: 4 Cov.: 33 AF XY: 0.00363 AC XY: 270 AN XY: 74474

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.00534

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00847 Hom.: 1

Bravo AF: 0.00195

Asia WGS AF: 0.000289 AC: 2 AN: 3478

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

GeneDx

Dec 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.57

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: rs544694134; hg19: chr19-46268598;