chr4-139889909-TTGCTGCTGC-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018717.5(MAML3):​c.1518_1526delGCAGCAGCA​(p.Gln507_Gln509del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00707 in 1,475,070 control chromosomes in the GnomAD database, including 339 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.077 ( 138 hom., cov: 0)
Exomes 𝑓: 0.0047 ( 201 hom. )

Consequence

MAML3
NM_018717.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.00
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 Benign. Variant got -8 ACMG points.

BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAML3NM_018717.5 linkc.1518_1526delGCAGCAGCA p.Gln507_Gln509del disruptive_inframe_deletion Exon 2 of 5 ENST00000509479.6 NP_061187.3 Q96JK9Q9NPV6
MAML3XM_047415929.1 linkc.1518_1526delGCAGCAGCA p.Gln507_Gln509del disruptive_inframe_deletion Exon 2 of 5 XP_047271885.1
MAML3XM_047415930.1 linkc.1518_1526delGCAGCAGCA p.Gln507_Gln509del disruptive_inframe_deletion Exon 2 of 3 XP_047271886.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAML3ENST00000509479.6 linkc.1518_1526delGCAGCAGCA p.Gln507_Gln509del disruptive_inframe_deletion Exon 2 of 5 1 NM_018717.5 ENSP00000421180.1 Q96JK9
MAML3ENST00000502696.1 linkc.109-159251_109-159243delGCAGCAGCA intron_variant Intron 1 of 3 2 ENSP00000422783.1 H0Y920

Frequencies

GnomAD3 genomes
AF:
0.0773
AC:
3689
AN:
47722
Hom.:
138
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.116
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0258
Gnomad ASJ
AF:
0.00896
Gnomad EAS
AF:
0.0221
Gnomad SAS
AF:
0.00936
Gnomad FIN
AF:
0.00120
Gnomad MID
AF:
0.0521
Gnomad NFE
AF:
0.0217
Gnomad OTH
AF:
0.0609
GnomAD3 exomes
AF:
0.00916
AC:
1567
AN:
171060
Hom.:
48
AF XY:
0.00801
AC XY:
750
AN XY:
93608
show subpopulations
Gnomad AFR exome
AF:
0.0731
Gnomad AMR exome
AF:
0.00947
Gnomad ASJ exome
AF:
0.00274
Gnomad EAS exome
AF:
0.0126
Gnomad SAS exome
AF:
0.00426
Gnomad FIN exome
AF:
0.000335
Gnomad NFE exome
AF:
0.00234
Gnomad OTH exome
AF:
0.00967
GnomAD4 exome
AF:
0.00471
AC:
6728
AN:
1427260
Hom.:
201
AF XY:
0.00444
AC XY:
3143
AN XY:
707132
show subpopulations
Gnomad4 AFR exome
AF:
0.0773
Gnomad4 AMR exome
AF:
0.00743
Gnomad4 ASJ exome
AF:
0.00145
Gnomad4 EAS exome
AF:
0.00956
Gnomad4 SAS exome
AF:
0.00301
Gnomad4 FIN exome
AF:
0.000325
Gnomad4 NFE exome
AF:
0.00248
Gnomad4 OTH exome
AF:
0.00820
GnomAD4 genome
AF:
0.0773
AC:
3696
AN:
47810
Hom.:
138
Cov.:
0
AF XY:
0.0733
AC XY:
1721
AN XY:
23484
show subpopulations
Gnomad4 AFR
AF:
0.116
Gnomad4 AMR
AF:
0.0254
Gnomad4 ASJ
AF:
0.00896
Gnomad4 EAS
AF:
0.0221
Gnomad4 SAS
AF:
0.00935
Gnomad4 FIN
AF:
0.00120
Gnomad4 NFE
AF:
0.0217
Gnomad4 OTH
AF:
0.0637

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