chr8-38107092-G-C

Variant names:

• chr8-38107092-G-C
• NM_004674.5:c.327G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004674.5(ASH2L):​c.327G>C​(p.Gln109His) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ASH2L NM_004674.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.30
• Publications: 0 publications found

Genes affected

ASH2L (HGNC:744): (ASH2 like, histone lysine methyltransferase complex subunit) Enables beta-catenin binding activity and transcription cis-regulatory region binding activity. Contributes to histone methyltransferase activity (H3-K4 specific). Involved in histone H3-K4 methylation; positive regulation of cell population proliferation; and response to estrogen. Acts upstream of or within cellular response to DNA damage stimulus. Located in nucleus. Part of MLL3/4 complex and Set1C/COMPASS complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2444596).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004674.5. 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
	ASH2L	NM_004674.5	MANE Select	c.327G>C	p.Gln109His	missense	Exon 3 of 16	NP_004665.2	Q9UBL3-1
	ASH2L	NM_001105214.2		c.45G>C	p.Gln15His	missense	Exon 3 of 16	NP_001098684.1	Q9UBL3-3
	ASH2L	NM_001261832.1		c.45G>C	p.Gln15His	missense	Exon 3 of 15	NP_001248761.1	Q9UBL3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASH2L	ENST00000343823.11	TSL:1 MANE Select	c.327G>C	p.Gln109His	missense	Exon 3 of 16	ENSP00000340896.5	Q9UBL3-1
	ASH2L	ENST00000428278.6	TSL:1	c.45G>C	p.Gln15His	missense	Exon 3 of 16	ENSP00000395310.2	Q9UBL3-3
	ASH2L	ENST00000521652.5	TSL:1	c.45G>C	p.Gln15His	missense	Exon 3 of 15	ENSP00000430259.1	Q9UBL3-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.23
Sift	Benign	0.057	T
Sift4G	Benign	0.088	T
Polyphen		0.0	B
Vest4		0.60
MutPred		0.29		Loss of disorder (P = 0.1666)
MVP		0.79
MPC		0.99
ClinPred		0.39	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.60
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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

hg19: chr8-37964610;