chr19-6218013-C-T

Variant names:

• chr19-6218013-C-T
• rs138601995
• NM_005934.4:c.1139G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005934.4(MLLT1):​c.1139G>A​(p.Ser380Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. S380T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MLLT1 NM_005934.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.96
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39414817).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005934.4. 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
	MLLT1	NM_005934.4	MANE Select	c.1139G>A	p.Ser380Asn	missense	Exon 7 of 12	NP_005925.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT1	ENST00000252674.9	TSL:1 MANE Select	c.1139G>A	p.Ser380Asn	missense	Exon 7 of 12	ENSP00000252674.6	Q03111
	MLLT1	ENST00000867663.1		c.1013G>A	p.Ser338Asn	missense	Exon 6 of 11	ENSP00000537722.1
	MLLT1	ENST00000943587.1		c.1010G>A	p.Ser337Asn	missense	Exon 6 of 11	ENSP00000613646.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.0
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.011	D
Polyphen		0.98	D
Vest4		0.39
MutPred		0.36		Loss of phosphorylation at S380 (P = 2e-04)
MVP		0.57
MPC		0.24
ClinPred		0.90	D
GERP RS		4.6
Varity_R		0.51
gMVP		0.27
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs138601995; hg19: chr19-6218024;