NM_018023.5:c.4033G>T

Variant names:

• chr3-183808051-G-T
• rs761313198
• NM_018023.5:c.4033G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_018023.5(YEATS2):​c.4033G>T​(p.Val1345Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000768 in 1,563,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1345M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: YEATS2 NM_018023.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.48
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20036057).
• BS2: High AC in GnomAdExome4 at 10 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.4033G>T	p.Val1345Leu	missense	Exon 29 of 31	NP_060493.3
	YEATS2	NM_001351370.2		c.4036G>T	p.Val1346Leu	missense	Exon 29 of 31	NP_001338299.1
	YEATS2	NM_001351369.2		c.4033G>T	p.Val1345Leu	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.4033G>T	p.Val1345Leu	missense	Exon 29 of 31	ENSP00000306983.5	Q9ULM3
	YEATS2	ENST00000884732.1		c.4036G>T	p.Val1346Leu	missense	Exon 29 of 31	ENSP00000554791.1
	YEATS2	ENST00000884736.1		c.4036G>T	p.Val1346Leu	missense	Exon 30 of 32	ENSP00000554795.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 172768 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000709 AC: 10 AN: 1411404 Hom.: 0 Cov.: 30 AF XY: 0.00000574 AC XY: 4 AN XY: 697314

African (AFR) AF: 0.00 AC: 0 AN: 32214

American (AMR) AF: 0.00 AC: 0 AN: 37466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25274

East Asian (EAS) AF: 0.00 AC: 0 AN: 36874

South Asian (SAS) AF: 0.00 AC: 0 AN: 79962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50174

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

European-Non Finnish (NFE) AF: 0.00000921 AC: 10 AN: 1085282

Other (OTH) AF: 0.00 AC: 0 AN: 58452

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.31
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.5
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.050	D
Sift4G	Benign	0.20	T
Polyphen		0.58	P
Vest4		0.16
MutPred		0.45		Loss of glycosylation at T1341 (P = 0.0539)
MVP		0.11
MPC		0.19
ClinPred		0.78	D
GERP RS		5.5
Varity_R		0.082
gMVP		0.57
Mutation Taster		=82/18	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: rs761313198; hg19: chr3-183525839;