Genetic Variant MMS22L:c.3650+1382C>T (chr6-97148471-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001350599.2(MMS22L):c.3650+1382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,010 control chromosomes in the GnomAD database, including 50,032 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 50032 hom., cov: 30)

Consequence

MMS22L
NM_001350599.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.296

Publications

2 publications found

Variant links:

Genes affected

MMS22L (HGNC:21475): (MMS22 like, DNA repair protein) The protein encoded by this gene forms a complex with tonsoku-like, DNA repair protein (TONSL), and this complex recognizes and repairs DNA double-strand breaks at sites of stalled or collapsed replication forks. The encoded protein also can bind with the histone-associated protein NFKBIL2 to help regulate the chromatin state at stalled replication forks. Finally, this gene appears to be overexpressed in most lung and esophageal cancers. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

MMS22L links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350599.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MMS22L	NM_001350599.2	MANE Select	c.3650+1382C>T	intron	N/A	NP_001337528.1	Q6ZRQ5
MMS22L	NM_198468.4		c.3650+1382C>T	intron	N/A	NP_940870.2	Q6ZRQ5
MMS22L	NM_001350600.2		c.2801+1382C>T	intron	N/A	NP_001337529.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MMS22L	ENST00000683635.1	MANE Select	c.3650+1382C>T	intron	N/A	ENSP00000508046.1	Q6ZRQ5
MMS22L	ENST00000275053.8	TSL:2	c.3650+1382C>T	intron	N/A	ENSP00000275053.4	Q6ZRQ5
MMS22L	ENST00000929352.1		c.3650+1382C>T	intron	N/A	ENSP00000599411.1

Frequencies

GnomAD3 genomes

AF:

0.804

AC:

122048

AN:

151892

Hom.:

49965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.949

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.823

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.875

Gnomad FIN

AF:

0.671

Gnomad MID

AF:

0.704

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.791

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.804

AC:

122175

AN:

152010

Hom.:

50032

Cov.:

AF XY:

0.808

AC XY:

60008

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.949

AC:

39373

AN:

41498

American (AMR)

AF:

0.823

AC:

12554

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.712

AC:

2468

AN:

3468

East Asian (EAS)

AF:

0.998

AC:

5163

AN:

5172

South Asian (SAS)

AF:

0.875

AC:

4218

AN:

4818

European-Finnish (FIN)

AF:

0.671

AC:

7072

AN:

10536

Middle Eastern (MID)

AF:

0.705

AC:

206

AN:

292

European-Non Finnish (NFE)

AF:

0.717

AC:

48707

AN:

67952

Other (OTH)

AF:

0.794

AC:

1674

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1140

2280

3421

4561

5701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.780

Hom.:

8139

Bravo

AF:

0.820

Asia WGS

AF:

0.946

AC:

3286

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.7

(source)

DANN

Benign

0.65

PhyloP100

-0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over