rs749203329

Variant names:

• chr19-6213787-C-A
• NM_005934.4:c.1418G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-6213787-C-A
• chr19-6213787-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_005934.4(MLLT1):​c.1418G>T​(p.Arg473Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,488 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R473Q) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MLLT1 NM_005934.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95

Genes affected

MLLT1 (HGNC:7134): (MLLT1 super elongation complex subunit) Predicted to be involved in regulation of transcription, DNA-templated. Predicted to act upstream of or within negative regulation of protein kinase activity. Located in cytosol; fibrillar center; and nucleoplasm. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr19-6213787-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 242890.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT1	NM_005934.4	c.1418G>T	p.Arg473Leu	missense_variant	Exon 10 of 12	ENST00000252674.9	NP_005925.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT1	ENST00000252674.9	c.1418G>T	p.Arg473Leu	missense_variant	Exon 10 of 12	1	NM_005934.4	ENSP00000252674.6
MLLT1	ENST00000585588.1	n.453G>T		non_coding_transcript_exon_variant	Exon 4 of 6	3		ENSP00000519594.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461488 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727076

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.17
Sift	Benign	0.14	T
Sift4G	Benign	0.31	T
Polyphen		0.99	D
Vest4		0.68
MutPred		0.33		Loss of methylation at R473 (P = 0.0238);
MVP		0.37
MPC		0.32
ClinPred		0.86	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-6213798;