rs2211243

Variant names:

• chr10-97496999-T-C
• rs2211243
• NM_022362.5:c.112+1274A>G

Variant summary

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

The NM_022362.5(MMS19):​c.112+1274A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,024 control chromosomes in the GnomAD database, including 23,429 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 0.55 (23429 hom., cov: 33)
• Consequence: MMS19 NM_022362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259
• Publications: 3 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMS19	NM_022362.5	c.112+1274A>G		intron_variant	Intron 1 of 30	ENST00000438925.7	NP_071757.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMS19	ENST00000438925.7	c.112+1274A>G		intron_variant	Intron 1 of 30	1	NM_022362.5	ENSP00000412698.2

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83361 AN: 151908 Hom.: 23383 Cov.: 33

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.549 AC: 83468 AN: 152024 Hom.: 23429 Cov.: 33 AF XY: 0.552 AC XY: 40981 AN XY: 74292

African (AFR) AF: 0.662 AC: 27472 AN: 41476

American (AMR) AF: 0.508 AC: 7764 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1696 AN: 3470

East Asian (EAS) AF: 0.610 AC: 3163 AN: 5184

South Asian (SAS) AF: 0.647 AC: 3118 AN: 4822

European-Finnish (FIN) AF: 0.501 AC: 5266 AN: 10518

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.490 AC: 33293 AN: 67966

Other (OTH) AF: 0.506 AC: 1070 AN: 2116

Alfa AF: 0.523 Hom.: 2647

Bravo AF: 0.546

Asia WGS AF: 0.628 AC: 2184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		0.26
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: rs2211243; hg19: chr10-99256756;