4-139889909-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018717.5(MAML3):​c.1515_1526dupGCAGCAGCAGCA​(p.Gln506_Gln509dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000065 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

MAML3
NM_018717.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.616
Variant links:
Genes affected
MAML3 (HGNC:16272): (mastermind like transcriptional coactivator 3) Enables transcription coactivator activity. Involved in Notch signaling pathway and positive regulation of transcription by RNA polymerase II. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAML3NM_018717.5 linkc.1515_1526dupGCAGCAGCAGCA p.Gln506_Gln509dup disruptive_inframe_insertion Exon 2 of 5 ENST00000509479.6 NP_061187.3 Q96JK9Q9NPV6
MAML3XM_047415929.1 linkc.1515_1526dupGCAGCAGCAGCA p.Gln506_Gln509dup disruptive_inframe_insertion Exon 2 of 5 XP_047271885.1
MAML3XM_047415930.1 linkc.1515_1526dupGCAGCAGCAGCA p.Gln506_Gln509dup disruptive_inframe_insertion Exon 2 of 3 XP_047271886.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAML3ENST00000509479.6 linkc.1515_1526dupGCAGCAGCAGCA p.Gln506_Gln509dup disruptive_inframe_insertion Exon 2 of 5 1 NM_018717.5 ENSP00000421180.1 Q96JK9
MAML3ENST00000502696.1 linkc.109-159254_109-159243dupGCAGCAGCAGCA intron_variant Intron 1 of 3 2 ENSP00000422783.1 H0Y920

Frequencies

GnomAD3 genomes
AF:
0.000502
AC:
24
AN:
47822
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000458
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000865
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00123
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000651
AC:
93
AN:
1428710
Hom.:
1
Cov.:
0
AF XY:
0.0000551
AC XY:
39
AN XY:
707940
show subpopulations
Gnomad4 AFR exome
AF:
0.0000305
Gnomad4 AMR exome
AF:
0.0000454
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000412
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000763
Gnomad4 NFE exome
AF:
0.0000599
Gnomad4 OTH exome
AF:
0.0000848
GnomAD4 genome
AF:
0.000502
AC:
24
AN:
47822
Hom.:
0
Cov.:
0
AF XY:
0.000554
AC XY:
13
AN XY:
23456
show subpopulations
Gnomad4 AFR
AF:
0.000458
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000865
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00123
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs58015886; hg19: chr4-140811063; API