chr16-58516208-T-A

Position:

• chr16-58516208-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001160305.4(SETD6):​c.341T>A​(p.Val114Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SETD6 NM_001160305.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0670

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03887233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETD6	NM_001160305.4	c.341T>A	p.Val114Asp	missense_variant	3/8	ENST00000219315.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETD6	ENST00000219315.9	c.341T>A	p.Val114Asp	missense_variant	3/8	1	NM_001160305.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.341T>A (p.V114D) alteration is located in exon 3 (coding exon 3) of the SETD6 gene. This alteration results from a T to A substitution at nucleotide position 341, causing the valine (V) at amino acid position 114 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.5
DANN	Benign	0.76
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.12
Sift	Benign	0.030	D
Sift4G	Benign	0.17	T
MutPred		0.23		Gain of catalytic residue at L42 (P = 4e-04);
MVP		0.014
ClinPred		0.091	T
GERP RS		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-58550112;