chr10-21534743-C-T

Variant names:

• chr10-21534743-C-T
• rs199515071
• NM_001195626.3:c.99C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001324297.2(MLLT10):​c.-977C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,613,122 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00025 (1 hom.)
• Consequence: MLLT10 NM_001324297.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.73
• Publications: 1 publications found

Genes affected

MLLT10 (HGNC:16063): (MLLT10 histone lysine methyltransferase DOT1L cofactor) This gene encodes a transcription factor and has been identified as a partner gene involved in several chromosomal rearrangements resulting in various leukemias. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 10-21534743-C-T is Benign according to our data. Variant chr10-21534743-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2640346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 31 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324297.2. 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
	MLLT10	NM_001195626.3	MANE Select	c.99C>T	p.Gly33Gly	synonymous	Exon 2 of 23	NP_001182555.1	P55197-4
	MLLT10	NM_001324297.2		c.-977C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 25	NP_001311226.1
	MLLT10	NM_004641.4		c.99C>T	p.Gly33Gly	synonymous	Exon 2 of 24	NP_004632.1	P55197-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT10	ENST00000307729.12	TSL:1 MANE Select	c.99C>T	p.Gly33Gly	synonymous	Exon 2 of 23	ENSP00000307411.7	P55197-4
	MLLT10	ENST00000377059.7	TSL:1	c.99C>T	p.Gly33Gly	synonymous	Exon 1 of 22	ENSP00000366258.4	P55197-4
	MLLT10	ENST00000377072.8	TSL:1	c.99C>T	p.Gly33Gly	synonymous	Exon 2 of 24	ENSP00000366272.3	P55197-1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 151942 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00491

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000332 AC: 83 AN: 250252 AF XY: 0.000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00597

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.000493

GnomAD4 exome AF: 0.000249 AC: 364 AN: 1461180 Hom.: 1 Cov.: 32 AF XY: 0.000253 AC XY: 184 AN XY: 726942

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.000179 AC: 8 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00620 AC: 162 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000145 AC: 161 AN: 1111554

Other (OTH) AF: 0.000530 AC: 32 AN: 60354

GnomAD4 genome AF: 0.000204 AC: 31 AN: 151942 Hom.: 0 Cov.: 30 AF XY: 0.000243 AC XY: 18 AN XY: 74184

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.000131 AC: 2 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00491 AC: 17 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67908

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000702 Hom.: 1

Bravo AF: 0.000200

EpiCase AF: 0.000273

EpiControl AF: 0.00

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	-0.34
CADD	Benign	16
DANN	Benign	0.97
PhyloP100		2.7
PromoterAI		-0.020	Neutral

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

Other links and lift over

dbSNP: rs199515071; hg19: chr10-21823672; COSMIC: COSV56990321; COSMIC: COSV56990321;