chr3-183808040-C-T

Variant names:

• chr3-183808040-C-T
• rs201018068
• NM_018023.5:c.4022C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018023.5(YEATS2):​c.4022C>T​(p.Thr1341Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000487 in 1,561,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: YEATS2 NM_018023.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

Genes affected

YEATS2 (HGNC:25489): (YEATS domain containing 2) Summary: The protein encoded by this gene is a scaffolding subunit of the ATAC complex, which is a complex with acetyltransferase activity on histones H3 and H4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2017]

YEATS2-AS1 (HGNC:41101): (YEATS2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008826822).
• BS2: High AC in GnomAdExome4 at 72 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018023.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YEATS2	NM_018023.5	MANE Select	c.4022C>T	p.Thr1341Ile	missense	Exon 29 of 31	NP_060493.3
	YEATS2	NM_001351370.2		c.4025C>T	p.Thr1342Ile	missense	Exon 29 of 31	NP_001338299.1
	YEATS2	NM_001351369.2		c.4022C>T	p.Thr1341Ile	missense	Exon 29 of 31	NP_001338298.1	Q9ULM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YEATS2	ENST00000305135.10	TSL:1 MANE Select	c.4022C>T	p.Thr1341Ile	missense	Exon 29 of 31	ENSP00000306983.5	Q9ULM3
	YEATS2	ENST00000884732.1		c.4025C>T	p.Thr1342Ile	missense	Exon 29 of 31	ENSP00000554791.1
	YEATS2	ENST00000884736.1		c.4025C>T	p.Thr1342Ile	missense	Exon 30 of 32	ENSP00000554795.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152116 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000111 AC: 19 AN: 170496 AF XY: 0.0000771

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00137

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000217

GnomAD4 exome AF: 0.0000511 AC: 72 AN: 1409540 Hom.: 0 Cov.: 30 AF XY: 0.0000488 AC XY: 34 AN XY: 696196

African (AFR) AF: 0.00 AC: 0 AN: 32158

American (AMR) AF: 0.00 AC: 0 AN: 37184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25252

East Asian (EAS) AF: 0.00182 AC: 67 AN: 36738

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084238

Other (OTH) AF: 0.0000685 AC: 4 AN: 58354

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74440

African (AFR) AF: 0.00 AC: 0 AN: 41544

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000769 AC: 9

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.064
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.031	D
Polyphen		0.0	B
Vest4		0.27
MutPred		0.43		Loss of glycosylation at T1341 (P = 0.0539)
MVP		0.043
MPC		0.11
ClinPred		0.054	T
GERP RS		4.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.093
gMVP		0.38
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs201018068; hg19: chr3-183525828;