4-139889909-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3BS1BS2

The NM_018717.5(MAML3):​c.1506_1526delGCAGCAGCAGCAGCAGCAGCA​(p.Gln503_Gln509del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00124 in 1,476,644 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 9 hom., cov: 0)
Exomes 𝑓: 0.00076 ( 4 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 -9 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_018717.5
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0153 (734/47904) while in subpopulation AFR AF= 0.024 (685/28494). AF 95% confidence interval is 0.0225. There are 9 homozygotes in gnomad4. There are 344 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAd4 at 734 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAML3NM_018717.5 linkc.1506_1526delGCAGCAGCAGCAGCAGCAGCA p.Gln503_Gln509del disruptive_inframe_deletion Exon 2 of 5 ENST00000509479.6 NP_061187.3 Q96JK9Q9NPV6
MAML3XM_047415929.1 linkc.1506_1526delGCAGCAGCAGCAGCAGCAGCA p.Gln503_Gln509del disruptive_inframe_deletion Exon 2 of 5 XP_047271885.1
MAML3XM_047415930.1 linkc.1506_1526delGCAGCAGCAGCAGCAGCAGCA p.Gln503_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.1506_1526delGCAGCAGCAGCAGCAGCAGCA p.Gln503_Gln509del disruptive_inframe_deletion Exon 2 of 5 1 NM_018717.5 ENSP00000421180.1 Q96JK9
MAML3ENST00000502696.1 linkc.109-159263_109-159243delGCAGCAGCAGCAGCAGCAGCA intron_variant Intron 1 of 3 2 ENSP00000422783.1 H0Y920

Frequencies

GnomAD3 genomes
AF:
0.0154
AC:
734
AN:
47816
Hom.:
9
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00243
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00389
Gnomad SAS
AF:
0.00390
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00191
Gnomad OTH
AF:
0.0140
GnomAD4 exome
AF:
0.000764
AC:
1091
AN:
1428740
Hom.:
4
AF XY:
0.000774
AC XY:
548
AN XY:
707954
show subpopulations
Gnomad4 AFR exome
AF:
0.0150
Gnomad4 AMR exome
AF:
0.000658
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00379
Gnomad4 SAS exome
AF:
0.00253
Gnomad4 FIN exome
AF:
0.0000191
Gnomad4 NFE exome
AF:
0.000143
Gnomad4 OTH exome
AF:
0.000831
GnomAD4 genome
AF:
0.0153
AC:
734
AN:
47904
Hom.:
9
Cov.:
0
AF XY:
0.0146
AC XY:
344
AN XY:
23534
show subpopulations
Gnomad4 AFR
AF:
0.0240
Gnomad4 AMR
AF:
0.00243
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00390
Gnomad4 SAS
AF:
0.00312
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00191
Gnomad4 OTH
AF:
0.0139

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