NM_018023.5:c.4033G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_018023.5(YEATS2):​c.4033G>A​(p.Val1345Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000179 in 1,563,516 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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. V1345L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (1 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3152762).
• BS2: High AC in GnomAdExome4 at 26 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>A	p.Val1345Met	missense	Exon 29 of 31	NP_060493.3
	YEATS2	NM_001351370.2		c.4036G>A	p.Val1346Met	missense	Exon 29 of 31	NP_001338299.1
	YEATS2	NM_001351369.2		c.4033G>A	p.Val1345Met	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>A	p.Val1345Met	missense	Exon 29 of 31	ENSP00000306983.5	Q9ULM3
	YEATS2	ENST00000884732.1		c.4036G>A	p.Val1346Met	missense	Exon 29 of 31	ENSP00000554791.1
	YEATS2	ENST00000884736.1		c.4036G>A	p.Val1346Met	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: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000347 AC: 6 AN: 172768 AF XY: 0.0000217

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: 0.0000623

Gnomad NFE exome AF: 0.0000281

Gnomad OTH exome AF: 0.000433

GnomAD4 exome AF: 0.0000184 AC: 26 AN: 1411404 Hom.: 1 Cov.: 30 AF XY: 0.0000215 AC XY: 15 AN XY: 697314

African (AFR) AF: 0.0000621 AC: 2 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: 0.0000199 AC: 1 AN: 50174

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5706

European-Non Finnish (NFE) AF: 0.0000147 AC: 16 AN: 1085282

Other (OTH) AF: 0.0000855 AC: 5 AN: 58452

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 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: 0.00316 AC: 1 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

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

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000341 AC: 4

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	0.15
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.20
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.36		Loss of glycosylation at T1341 (P = 0.0539)
MVP		0.13
MPC		0.49
ClinPred		0.31	T
GERP RS		5.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.074
gMVP		0.58
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;