rs2236575

Variant names:

• chr10-97465981-T-A
• rs2236575
• NM_022362.5:c.1607-27A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-97465981-T-A
• chr10-97465981-T-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.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
• Publications: 15 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 rank	MANE	Protein	UniProt
MMS19	NM_022362.5	c.1607-27A>T		intron_variant	Intron 17 of 30	ENST00000438925.7	NP_071757.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMS19	ENST00000438925.7	c.1607-27A>T		intron_variant	Intron 17 of 30	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

GnomAD2 exomes AF: 0.420 AC: 104565 AN: 249192 AF XY: 0.418

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 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

African (AFR) AF: 0.367 AC: 12281 AN: 33462

American (AMR) AF: 0.482 AC: 21555 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 10791 AN: 26062

East Asian (EAS) AF: 0.400 AC: 15863 AN: 39682

South Asian (SAS) AF: 0.347 AC: 29877 AN: 86172

European-Finnish (FIN) AF: 0.392 AC: 20917 AN: 53332

Middle Eastern (MID) AF: 0.442 AC: 2547 AN: 5768

European-Non Finnish (NFE) AF: 0.434 AC: 482337 AN: 1110520

Other (OTH) AF: 0.420 AC: 25328 AN: 60304

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

African (AFR) AF: 0.365 AC: 15133 AN: 41470

American (AMR) AF: 0.416 AC: 6362 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1990 AN: 5154

South Asian (SAS) AF: 0.337 AC: 1622 AN: 4816

European-Finnish (FIN) AF: 0.382 AC: 4043 AN: 10578

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.430 AC: 29218 AN: 67952

Other (OTH) AF: 0.437 AC: 922 AN: 2110

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
PhyloP100		-0.091
La Branchor		0.46
BranchPoint Hunter		3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236575; hg19: chr10-99225738; COSMIC: COSV59134377; COSMIC: COSV59134377;