4-139889909-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant summary

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

The NM_018717.5(MAML3):​c.1521_1526dupGCAGCA​(p.Gln508_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 0.0039 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0012 ( 36 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 186 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAML3NM_018717.5 linkc.1521_1526dupGCAGCA p.Gln508_Gln509dup disruptive_inframe_insertion Exon 2 of 5 ENST00000509479.6 NP_061187.3 Q96JK9Q9NPV6
MAML3XM_047415929.1 linkc.1521_1526dupGCAGCA p.Gln508_Gln509dup disruptive_inframe_insertion Exon 2 of 5 XP_047271885.1
MAML3XM_047415930.1 linkc.1521_1526dupGCAGCA p.Gln508_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.1521_1526dupGCAGCA p.Gln508_Gln509dup disruptive_inframe_insertion Exon 2 of 5 1 NM_018717.5 ENSP00000421180.1 Q96JK9
MAML3ENST00000502696.1 linkc.109-159248_109-159243dupGCAGCA intron_variant Intron 1 of 3 2 ENSP00000422783.1 H0Y920

Frequencies

GnomAD3 genomes
AF:
0.00385
AC:
184
AN:
47818
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00151
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00206
Gnomad ASJ
AF:
0.0328
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000780
Gnomad FIN
AF:
0.00120
Gnomad MID
AF:
0.0104
Gnomad NFE
AF:
0.0135
Gnomad OTH
AF:
0.00776
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00125
AC:
1782
AN:
1428132
Hom.:
36
Cov.:
0
AF XY:
0.00118
AC XY:
833
AN XY:
707644
show subpopulations
Gnomad4 AFR exome
AF:
0.00101
Gnomad4 AMR exome
AF:
0.000544
Gnomad4 ASJ exome
AF:
0.00483
Gnomad4 EAS exome
AF:
0.0000515
Gnomad4 SAS exome
AF:
0.000281
Gnomad4 FIN exome
AF:
0.000382
Gnomad4 NFE exome
AF:
0.00137
Gnomad4 OTH exome
AF:
0.00112
GnomAD4 genome
AF:
0.00388
AC:
186
AN:
47906
Hom.:
0
Cov.:
0
AF XY:
0.00353
AC XY:
83
AN XY:
23534
show subpopulations
Gnomad4 AFR
AF:
0.00158
Gnomad4 AMR
AF:
0.00205
Gnomad4 ASJ
AF:
0.0328
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000779
Gnomad4 FIN
AF:
0.00120
Gnomad4 NFE
AF:
0.0135
Gnomad4 OTH
AF:
0.00772

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