Genetic Variant MMS19:c.1913-236T>C (chr10-97462918-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_022362.5(MMS19):c.1913-236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 418,804 control chromosomes in the GnomAD database, including 14,378 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 0.25 ( 4888 hom., cov: 32)

Exomes 𝑓: 0.25 ( 9490 hom. )

Consequence

MMS19
NM_022362.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.812

Publications

6 publications found

Variant links:

Genes affected

MMS19 (HGNC:13824): (MMS19 homolog, cytosolic iron-sulfur assembly component) Enables estrogen receptor binding activity and transcription coactivator activity. Involved in several processes, including iron-sulfur cluster assembly; positive regulation of nucleobase-containing compound metabolic process; and protein maturation by iron-sulfur cluster transfer. Located in cytosol; nucleoplasm; and spindle. Part of CIA complex and MMXD complex. [provided by Alliance of Genome Resources, Apr 2022]

MMS19 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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022362.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MMS19	NM_022362.5	MANE Select	c.1913-236T>C	intron	N/A	NP_071757.4
MMS19	NM_001351356.2		c.2030-236T>C	intron	N/A	NP_001338285.1
MMS19	NM_001289405.2		c.1913-236T>C	intron	N/A	NP_001276334.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MMS19	ENST00000438925.7	TSL:1 MANE Select	c.1913-236T>C	intron	N/A	ENSP00000412698.2
MMS19	ENST00000370782.6	TSL:1	c.1913-236T>C	intron	N/A	ENSP00000359818.1
MMS19	ENST00000355839.10	TSL:1	c.1784-236T>C	intron	N/A	ENSP00000348097.6

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37413

AN:

151968

Hom.:

4881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.245

GnomAD4 exome

AF:

0.251

AC:

66914

AN:

266718

Hom.:

9490

Cov.:

AF XY:

0.253

AC XY:

34686

AN XY:

137238

show subpopulations

African (AFR)

AF:

0.199

AC:

1488

AN:

7482

American (AMR)

AF:

0.274

AC:

2403

AN:

8764

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

3214

AN:

9376

East Asian (EAS)

AF:

0.469

AC:

10043

AN:

21404

South Asian (SAS)

AF:

0.282

AC:

3330

AN:

11826

European-Finnish (FIN)

AF:

0.225

AC:

4528

AN:

20130

Middle Eastern (MID)

AF:

0.252

AC:

351

AN:

1392

European-Non Finnish (NFE)

AF:

0.220

AC:

37146

AN:

169198

Other (OTH)

AF:

0.257

AC:

4411

AN:

17146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2243

4487

6730

8974

11217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

224

448

672

896

1120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.246

AC:

37431

AN:

152086

Hom.:

4888

Cov.:

AF XY:

0.250

AC XY:

18549

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.211

AC:

8735

AN:

41488

American (AMR)

AF:

0.301

AC:

4594

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

1236

AN:

3472

East Asian (EAS)

AF:

0.477

AC:

2470

AN:

5180

South Asian (SAS)

AF:

0.348

AC:

1678

AN:

4816

European-Finnish (FIN)

AF:

0.225

AC:

2375

AN:

10560

Middle Eastern (MID)

AF:

0.312

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.226

AC:

15359

AN:

67992

Other (OTH)

AF:

0.245

AC:

518

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1407

2814

4222

5629

7036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.122

Hom.:

209

Bravo

AF:

0.249

Asia WGS

AF:

0.407

AC:

1416

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.81

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over