NM_022362.5:c.1913-236T>C

Variant names:

• chr10-97462918-A-G
• rs29001322
• NM_022362.5:c.1913-236T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812
• Publications: 6 publications found

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]

ACMG classification

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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.: 32

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.: 0 AF XY: 0.253 AC XY: 34686 AN XY: 137238

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

GnomAD4 genome AF: 0.246 AC: 37431 AN: 152086 Hom.: 4888 Cov.: 32 AF XY: 0.250 AC XY: 18549 AN XY: 74310

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: 91 AN: 292

European-Non Finnish (NFE) AF: 0.226 AC: 15359 AN: 67992

Other (OTH) AF: 0.245 AC: 518 AN: 2110

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	11
DANN	Benign	0.81
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs29001322; hg19: chr10-99222675;