Genetic Variant NM_004674.5:c.107C>T (chr8-38105657-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_004674.5(ASH2L):c.107C>T(p.Ala36Val) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ASH2L
NM_004674.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.167

Publications

0 publications found

Variant links:

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]

ASH2L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08006477).

BP6

Variant 8-38105657-C-T is Benign according to our data. Variant chr8-38105657-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2321422.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASH2L	NM_004674.5	MANE Select	c.107C>T	p.Ala36Val	missense	Exon 1 of 16	NP_004665.2	Q9UBL3-1
ASH2L	NM_001282272.1		c.-165C>T		5_prime_UTR	Exon 1 of 15	NP_001269201.1	B4DPT1
ASH2L	NM_001105214.2		c.-577C>T		upstream_gene	N/A	NP_001098684.1	Q9UBL3-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASH2L	ENST00000343823.11	TSL:1 MANE Select	c.107C>T	p.Ala36Val	missense	Exon 1 of 16	ENSP00000340896.5	Q9UBL3-1
ASH2L	ENST00000899871.1		c.107C>T	p.Ala36Val	missense	Exon 1 of 16	ENSP00000569930.1
ASH2L	ENST00000971642.1		c.107C>T	p.Ala36Val	missense	Exon 1 of 16	ENSP00000641701.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1440368

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715942

African (AFR)

AF:

0.00

AC:

AN:

32176

American (AMR)

AF:

0.00

AC:

AN:

40624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24706

East Asian (EAS)

AF:

0.00

AC:

AN:

38942

South Asian (SAS)

AF:

0.00

AC:

AN:

83938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5000

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103536

Other (OTH)

AF:

0.00

AC:

AN:

59250

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.69

M_CAP

Benign

0.023

MetaRNN

Benign

0.080

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.17

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.20

REVEL

Benign

0.12

Sift

Benign

0.22

Sift4G

Uncertain

0.042

Polyphen

0.0

Vest4

0.037

MutPred

0.21

Gain of sheet (P = 0.0149)

MVP

0.54

MPC

0.011

ClinPred

0.13

GERP RS

-0.61

PromoterAI

0.025

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.038

gMVP

0.14

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over