10-21651678-T-C

Variant names:

• chr10-21651678-T-C
• rs370897151
• NM_001195626.3:c.705T>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.705T>C​(p.Tyr235Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,611,618 control chromosomes in the GnomAD database, including 2 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 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (2 hom.)
• Consequence: MLLT10 NM_001195626.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.601
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 10-21651678-T-C is Benign according to our data. Variant chr10-21651678-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3037162.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.601 with no splicing effect.
• BS2: High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.705T>C	p.Tyr235Tyr	synonymous_variant	Exon 9 of 23	ENST00000307729.12	NP_001182555.1
MLLT10	NM_004641.4	c.705T>C	p.Tyr235Tyr	synonymous_variant	Exon 9 of 24		NP_004632.1
MLLT10	NR_136736.2	n.1172T>C		non_coding_transcript_exon_variant	Exon 10 of 26
MLLT10	NM_001324297.2	c.-167T>C		5_prime_UTR_variant	Exon 10 of 25		NP_001311226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.705T>C	p.Tyr235Tyr	synonymous_variant	Exon 9 of 23	1	NM_001195626.3	ENSP00000307411.7

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000606 AC: 152 AN: 250804 AF XY: 0.000737

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000258 AC: 377 AN: 1459388 Hom.: 2 Cov.: 30 AF XY: 0.000346 AC XY: 251 AN XY: 726054

African (AFR) AF: 0.0000598 AC: 2 AN: 33434

American (AMR) AF: 0.0000899 AC: 4 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00352 AC: 302 AN: 85908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5746

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1110436

Other (OTH) AF: 0.000531 AC: 32 AN: 60276

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74434

African (AFR) AF: 0.00 AC: 0 AN: 41536

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000756 Hom.: 0

Bravo AF: 0.000102

Asia WGS AF: 0.00231 AC: 8 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MLLT10-related disorder Benign:1

Apr 09, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.0
DANN	Benign	0.42
PhyloP100		-0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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: rs370897151; hg19: chr10-21940607;