rs111826855

Positions:

• chr7-152358656-T-A
• chr7-152358656-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_170606.3(KMT2C):​c.181A>T​(p.Thr61Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: KMT2C NM_170606.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

Genes affected

KMT2C (HGNC:13726): (lysine methyltransferase 2C) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a nuclear protein with an AT hook DNA-binding domain, a DHHC-type zinc finger, six PHD-type zinc fingers, a SET domain, a post-SET domain and a RING-type zinc finger. This protein is a member of the ASC-2/NCOA6 complex (ASCOM), which possesses histone methylation activity and is involved in transcriptional coactivation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041053623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT2C	NM_170606.3	c.181A>T	p.Thr61Ser	missense_variant	2/59	ENST00000262189.11	NP_733751.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT2C	ENST00000262189.11	c.181A>T	p.Thr61Ser	missense_variant	2/59	1	NM_170606.3	ENSP00000262189.6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151840 Hom.: 0 Cov.: 32 FAILED QC

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151840 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74160

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.48
DEOGEN2	Benign	0.048	T;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.52	.;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.041	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.090	N;N;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.48	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.62	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.16
MutPred		0.13		Loss of solvent accessibility (P = 0.0561);Loss of solvent accessibility (P = 0.0561);Loss of solvent accessibility (P = 0.0561);
MVP		0.11
MPC		0.20
ClinPred		0.10	T
GERP RS		1.1
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.035
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-152055741;