16-58519444-T-C

Position:

• chr16-58519444-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001160305.4(SETD6):​c.*415T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 175,144 control chromosomes in the GnomAD database, including 5,983 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5046 hom., cov: 32)
  • Exomes 𝑓: 0.27 (937 hom.)
• Consequence: SETD6 NM_001160305.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

Genes affected

SETD6 (HGNC:26116): (SET domain containing 6, protein lysine methyltransferase) This gene encodes a methyltransferase that adds a methyl group to the histone H2AZ, which is involved in nuclear receptor-dependent transcription. The protein also interacts with several endogenous proteins which are involved in nuclear hormone receptor signaling. A related pseudogene is located on chromosome 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD6	NM_001160305.4	c.*415T>C		3_prime_UTR_variant	8/8	ENST00000219315.9	NP_001153777.1
SETD6	NM_024860.3	c.*415T>C		3_prime_UTR_variant	9/9		NP_079136.2
SETD6	NR_134583.1	n.1855T>C		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD6	ENST00000219315.9	c.*415T>C		3_prime_UTR_variant	8/8	1	NM_001160305.4	ENSP00000219315

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37480 AN: 151950 Hom.: 5031 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.267 AC: 6162 AN: 23076 Hom.: 937 Cov.: 0 AF XY: 0.272 AC XY: 3329 AN XY: 12252

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.367

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.247 AC: 37521 AN: 152068 Hom.: 5046 Cov.: 32 AF XY: 0.252 AC XY: 18763 AN XY: 74352

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.238

Alfa AF: 0.256 Hom.: 5282

Bravo AF: 0.247

Asia WGS AF: 0.353 AC: 1229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.51
DANN	Benign	0.45

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: rs37036; hg19: chr16-58553348;