NM_182931.3:c.99G>C

Variant names:

• chr7-105062191-G-C
• NM_182931.3:c.99G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_182931.3(KMT2E):​c.99G>C​(p.Val33Val) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KMT2E NM_182931.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.78
• Publications: 0 publications found

Genes affected

KMT2E (HGNC:18541): (lysine methyltransferase 2E (inactive)) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a protein with an N-terminal PHD zinc finger and a central SET domain. Overexpression of the protein inhibits cell cycle progression. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

KMT2E Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• O'Donnell-Luria-Rodan syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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 (BayesDel_noAF=-0.38).
• BP6: Variant 7-105062191-G-C is Benign according to our data. Variant chr7-105062191-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2754450.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182931.3. 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
	KMT2E	NM_182931.3	MANE Select	c.99G>C	p.Val33Val	synonymous	Exon 4 of 27	NP_891847.1	Q8IZD2-1
	KMT2E	NM_018682.4		c.99G>C	p.Val33Val	synonymous	Exon 3 of 26	NP_061152.3
	KMT2E	NM_001410908.1		c.99G>C	p.Val33Val	synonymous	Exon 3 of 25	NP_001397837.1	Q8IZD2-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMT2E	ENST00000311117.8	TSL:1 MANE Select	c.99G>C	p.Val33Val	synonymous	Exon 4 of 27	ENSP00000312379.3	Q8IZD2-1
	KMT2E	ENST00000473063.2	TSL:1	c.99G>C	p.Val33Val	synonymous	Exon 3 of 25	ENSP00000417156.2	Q8IZD2-7
	KMT2E	ENST00000476671.5	TSL:1	c.99G>C	p.Val33Val	synonymous	Exon 4 of 15	ENSP00000417888.1	Q8IZD2-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr7-104702638;