17-38711996-C-T

Variant names:

• chr17-38711996-C-T
• rs146464000
• NM_005937.4:c.702C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_005937.4(MLLT6):​c.702C>T​(p.His234His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,590,304 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (45 hom.)
• Consequence: MLLT6 NM_005937.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.457
• Publications: 1 publications found

Genes affected

MLLT6 (HGNC:7138): (MLLT6, PHD finger containing) Enables histone binding activity and nucleosome binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including negative regulation of histone H3-K79 methylation; renal potassium excretion; and renal sodium excretion. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 17-38711996-C-T is Benign according to our data. Variant chr17-38711996-C-T is described in ClinVar as [Benign]. Clinvar id is 787451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.457 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.012 (1823/152184) while in subpopulation AFR AF = 0.0417 (1732/41524). AF 95% confidence interval is 0.0401. There are 35 homozygotes in GnomAd4. There are 866 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1823 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT6	NM_005937.4	c.702C>T	p.His234His	synonymous_variant	Exon 7 of 20	ENST00000621332.5	NP_005928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT6	ENST00000621332.5	c.702C>T	p.His234His	synonymous_variant	Exon 7 of 20	1	NM_005937.4	ENSP00000479910.1
MLLT6	ENST00000620609.4	c.702C>T	p.His234His	synonymous_variant	Exon 7 of 9	1		ENSP00000482928.1
MLLT6	ENST00000620482.4	n.715C>T		non_coding_transcript_exon_variant	Exon 7 of 9	1
MLLT6	ENST00000618652.1	n.441C>T		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1820 AN: 152066 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00576

GnomAD2 exomes AF: 0.00315 AC: 725 AN: 230104 AF XY: 0.00212

Gnomad AFR exome AF: 0.0425

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000574

Gnomad OTH exome AF: 0.000361

GnomAD4 exome AF: 0.00122 AC: 1758 AN: 1438120 Hom.: 45 Cov.: 32 AF XY: 0.00106 AC XY: 757 AN XY: 713858

African (AFR) AF: 0.0442 AC: 1446 AN: 32678

American (AMR) AF: 0.00192 AC: 80 AN: 41746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24736

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38884

South Asian (SAS) AF: 0.000156 AC: 13 AN: 83102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52792

Middle Eastern (MID) AF: 0.00160 AC: 9 AN: 5636

European-Non Finnish (NFE) AF: 0.0000218 AC: 24 AN: 1099250

Other (OTH) AF: 0.00312 AC: 185 AN: 59296

GnomAD4 genome AF: 0.0120 AC: 1823 AN: 152184 Hom.: 35 Cov.: 32 AF XY: 0.0116 AC XY: 866 AN XY: 74424

African (AFR) AF: 0.0417 AC: 1732 AN: 41524

American (AMR) AF: 0.00490 AC: 75 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67986

Other (OTH) AF: 0.00570 AC: 12 AN: 2106

Alfa AF: 0.00686 Hom.: 8

Bravo AF: 0.0132

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.29
DANN	Benign	0.88
PhyloP100		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs146464000; hg19: chr17-36868249;