rs9388768

Variant names:

• chr6-130052957-C-A
• rs9388768
• NM_032438.4:c.548C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-130052957-C-A
• chr6-130052957-C-G
• chr6-130052957-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032438.4(L3MBTL3):​c.548C>A​(p.Thr183Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,611,926 control chromosomes in the GnomAD database, including 346,134 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (25359 hom., cov: 32)
  • Exomes 𝑓: 0.66 (320775 hom.)
• Consequence: L3MBTL3 NM_032438.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.15
• Publications: 49 publications found

Genes affected

L3MBTL3 (HGNC:23035): (L3MBTL histone methyl-lysine binding protein 3) This gene encodes a member of the malignant brain tumor (MBT) family of chromatin interacting transcriptional repressors. Members of this family function as methyl-lysine readers, which recognize methylated lysine residues on histone protein tails, and are associated with the repression of gene expression. The encoded protein may regulate hematopoiesis. Homozygous deletion of this gene has been observed in human patients with medulloblastoma. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.322221E-6).
• BP6: Variant 6-130052957-C-A is Benign according to our data. Variant chr6-130052957-C-A is described in ClinVar as Benign. ClinVar VariationId is 1266479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032438.4. 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
	L3MBTL3	NM_032438.4	MANE Select	c.548C>A	p.Thr183Asn	missense	Exon 7 of 23	NP_115814.1	Q96JM7-1
	L3MBTL3	NM_001007102.4		c.473C>A	p.Thr158Asn	missense	Exon 6 of 22	NP_001007103.1	Q96JM7-2
	L3MBTL3	NM_001346550.2		c.473C>A	p.Thr158Asn	missense	Exon 6 of 22	NP_001333479.1	Q96JM7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L3MBTL3	ENST00000361794.7	TSL:5 MANE Select	c.548C>A	p.Thr183Asn	missense	Exon 7 of 23	ENSP00000354526.2	Q96JM7-1
	L3MBTL3	ENST00000533560.5	TSL:1	c.473C>A	p.Thr158Asn	missense	Exon 6 of 22	ENSP00000437185.1	Q96JM7-2
	L3MBTL3	ENST00000858931.1		c.653C>A	p.Thr218Asn	missense	Exon 7 of 23	ENSP00000528990.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81548 AN: 151840 Hom.: 25358 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.576

GnomAD2 exomes AF: 0.638 AC: 160163 AN: 250858 AF XY: 0.644

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.662

Gnomad ASJ exome AF: 0.682

Gnomad EAS exome AF: 0.769

Gnomad FIN exome AF: 0.669

Gnomad NFE exome AF: 0.676

Gnomad OTH exome AF: 0.653

GnomAD4 exome AF: 0.658 AC: 959993 AN: 1459968 Hom.: 320775 Cov.: 39 AF XY: 0.657 AC XY: 477515 AN XY: 726340

African (AFR) AF: 0.179 AC: 5995 AN: 33468

American (AMR) AF: 0.655 AC: 29287 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 17805 AN: 26118

East Asian (EAS) AF: 0.722 AC: 28674 AN: 39688

South Asian (SAS) AF: 0.599 AC: 51602 AN: 86196

European-Finnish (FIN) AF: 0.670 AC: 35800 AN: 53396

Middle Eastern (MID) AF: 0.664 AC: 3830 AN: 5766

European-Non Finnish (NFE) AF: 0.674 AC: 748100 AN: 1110332

Other (OTH) AF: 0.645 AC: 38900 AN: 60322

GnomAD4 genome AF: 0.537 AC: 81560 AN: 151958 Hom.: 25359 Cov.: 32 AF XY: 0.540 AC XY: 40106 AN XY: 74278

African (AFR) AF: 0.196 AC: 8100 AN: 41384

American (AMR) AF: 0.626 AC: 9569 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2356 AN: 3468

East Asian (EAS) AF: 0.762 AC: 3934 AN: 5166

South Asian (SAS) AF: 0.587 AC: 2827 AN: 4814

European-Finnish (FIN) AF: 0.661 AC: 6979 AN: 10566

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45871 AN: 67966

Other (OTH) AF: 0.578 AC: 1220 AN: 2112

Alfa AF: 0.629 Hom.: 103472

Bravo AF: 0.523

TwinsUK AF: 0.673 AC: 2496

ALSPAC AF: 0.674 AC: 2596

ESP6500AA AF: 0.212 AC: 934

ESP6500EA AF: 0.681 AC: 5856

ExAC AF: 0.626 AC: 76036

Asia WGS AF: 0.644 AC: 2240 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.033
Sift	Benign	0.10	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.017
MPC		0.27
ClinPred		0.0066	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.065
gMVP		0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs9388768; hg19: chr6-130374102; COSMIC: COSV62384726; COSMIC: COSV62384726;