rs2236575

Positions:

• chr10-97465981-T-A
• chr10-97465981-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022362.5(MMS19):​c.1607-27A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,612,030 control chromosomes in the GnomAD database, including 145,455 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.40 (12290 hom., cov: 33)
  • Exomes 𝑓: 0.43 (133165 hom.)
• Consequence: MMS19 NM_022362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

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: This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMS19	NM_022362.5	c.1607-27A>T		intron_variant		ENST00000438925.7	NP_071757.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMS19	ENST00000438925.7	c.1607-27A>T		intron_variant		1	NM_022362.5	ENSP00000412698.2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61071 AN: 151918 Hom.: 12292 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.435

GnomAD3 exomes AF: 0.420 AC: 104565 AN: 249192 Hom.: 22313 AF XY: 0.418 AC XY: 56207 AN XY: 134604

Gnomad AFR exome AF: 0.365

Gnomad AMR exome AF: 0.490

Gnomad ASJ exome AF: 0.411

Gnomad EAS exome AF: 0.398

Gnomad SAS exome AF: 0.348

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.436

GnomAD4 exome AF: 0.426 AC: 621496 AN: 1459994 Hom.: 133165 Cov.: 36 AF XY: 0.424 AC XY: 307699 AN XY: 726262

Gnomad4 AFR exome AF: 0.367

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.434

Gnomad4 OTH exome AF: 0.420

GnomAD4 genome AF: 0.402 AC: 61085 AN: 152036 Hom.: 12290 Cov.: 33 AF XY: 0.399 AC XY: 29617 AN XY: 74302

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.437

Alfa AF: 0.355 Hom.: 1591

Bravo AF: 0.411

Asia WGS AF: 0.359 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.67
La Branchor		0.46
BranchPoint Hunter		3.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2236575; hg19: chr10-99225738; COSMIC: COSV59134377; COSMIC: COSV59134377;