10-21673498-T-C

Variant names:

• chr10-21673498-T-C
• rs201326052
• NM_001195626.3:c.1200T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001195626.3(MLLT10):​c.1200T>C​(p.His400His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,613,850 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: MLLT10 NM_001195626.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.07
• Publications: 0 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]

ENSG00000304565 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 10-21673498-T-C is Benign according to our data. Variant chr10-21673498-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3050599.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.07 with no splicing effect.
• BS2: High AC in GnomAd4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195626.3. 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
	MLLT10	NM_001195626.3	MANE Select	c.1200T>C	p.His400His	synonymous	Exon 11 of 23	NP_001182555.1	P55197-4
	MLLT10	NM_004641.4		c.1200T>C	p.His400His	synonymous	Exon 11 of 24	NP_004632.1	P55197-1
	MLLT10	NM_001324297.2		c.465T>C	p.His155His	synonymous	Exon 13 of 25	NP_001311226.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT10	ENST00000307729.12	TSL:1 MANE Select	c.1200T>C	p.His400His	synonymous	Exon 11 of 23	ENSP00000307411.7	P55197-4
	MLLT10	ENST00000377059.7	TSL:1	c.1200T>C	p.His400His	synonymous	Exon 10 of 22	ENSP00000366258.4	P55197-4
	MLLT10	ENST00000377072.8	TSL:1	c.1200T>C	p.His400His	synonymous	Exon 11 of 24	ENSP00000366272.3	P55197-1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 151888 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000756 AC: 19 AN: 251310 AF XY: 0.0000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000174 AC: 255 AN: 1461846 Hom.: 1 Cov.: 35 AF XY: 0.000168 AC XY: 122 AN XY: 727222

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.000214 AC: 238 AN: 1111994

Other (OTH) AF: 0.000215 AC: 13 AN: 60390

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152004 Hom.: 0 Cov.: 31 AF XY: 0.000148 AC XY: 11 AN XY: 74298

African (AFR) AF: 0.0000965 AC: 4 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000180 Hom.: 0

Bravo AF: 0.0000907

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MLLT10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Benign	0.63
PhyloP100		2.1
PromoterAI		0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

dbSNP: rs201326052; hg19: chr10-21962427; COSMIC: COSV57000972; COSMIC: COSV57000972;