10-97462918-A-G

Position:

• chr10-97462918-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMS19	NM_022362.5	c.1913-236T>C		intron_variant		ENST00000438925.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMS19	ENST00000438925.7	c.1913-236T>C		intron_variant		1	NM_022362.5	P1

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

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.469

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.257

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

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.245

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs29001322; hg19: chr10-99222675;