16-58516292-C-T

Variant names:

• chr16-58516292-C-T
• rs200835277
• NM_001160305.4:c.425C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001160305.4(SETD6):​c.425C>T​(p.Pro142Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,452,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SETD6 NM_001160305.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.80

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.884

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETD6	NM_001160305.4	c.425C>T	p.Pro142Leu	missense_variant	Exon 3 of 8	ENST00000219315.9	NP_001153777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETD6	ENST00000219315.9	c.425C>T	p.Pro142Leu	missense_variant	Exon 3 of 8	1	NM_001160305.4	ENSP00000219315.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000418 AC: 1 AN: 239020 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 131412

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452840 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 723190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;.;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.2	.;.;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-7.2	D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.67
MutPred		0.87		.;.;Gain of MoRF binding (P = 0.0575);
MVP		0.54
MPC		0.73
ClinPred		0.98	D
GERP RS		3.2
Varity_R		0.54
gMVP		0.77

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: rs200835277; hg19: chr16-58550196;