10-97476460-C-G

Variant names:

• chr10-97476460-C-G
• rs872106
• NM_022362.5:c.684+223G>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.684+223G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,144 control chromosomes in the GnomAD database, including 4,207 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 0.23 (4207 hom., cov: 32)
• Consequence: MMS19 NM_022362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMS19	NM_022362.5	MANE Select	c.684+223G>C		intron	N/A	NP_071757.4
	MMS19	NM_001351356.2		c.801+223G>C		intron	N/A	NP_001338285.1
	MMS19	NM_001289405.2		c.684+223G>C		intron	N/A	NP_001276334.1	Q96T76-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMS19	ENST00000438925.7	TSL:1 MANE Select	c.684+223G>C		intron	N/A	ENSP00000412698.2	Q96T76-1
	MMS19	ENST00000370782.6	TSL:1	c.684+223G>C		intron	N/A	ENSP00000359818.1	Q96T76-1
	MMS19	ENST00000355839.10	TSL:1	c.555+223G>C		intron	N/A	ENSP00000348097.6	Q96T76-9

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34381 AN: 152026 Hom.: 4206 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0356

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.226 AC: 34404 AN: 152144 Hom.: 4207 Cov.: 32 AF XY: 0.226 AC XY: 16823 AN XY: 74370

African (AFR) AF: 0.173 AC: 7162 AN: 41502

American (AMR) AF: 0.213 AC: 3263 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3470

East Asian (EAS) AF: 0.0358 AC: 186 AN: 5190

South Asian (SAS) AF: 0.205 AC: 987 AN: 4820

European-Finnish (FIN) AF: 0.297 AC: 3144 AN: 10570

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18364 AN: 67986

Other (OTH) AF: 0.209 AC: 441 AN: 2108

Alfa AF: 0.163 Hom.: 348

Bravo AF: 0.212

Asia WGS AF: 0.138 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.64
PhyloP100		0.021
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: rs872106; hg19: chr10-99236217;