10-97489748-T-C

Variant names:

• chr10-97489748-T-C
• rs4917772
• NM_022362.5:c.113-5597A>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.113-5597A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,158 control chromosomes in the GnomAD database, including 6,110 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 0.28 (6110 hom., cov: 32)
• Consequence: MMS19 NM_022362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 2 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMS19	NM_022362.5	c.113-5597A>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.113-5597A>G		intron_variant	Intron 1 of 30	1	NM_022362.5	ENSP00000412698.2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42179 AN: 152040 Hom.: 6104 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.277 AC: 42205 AN: 152158 Hom.: 6110 Cov.: 32 AF XY: 0.280 AC XY: 20856 AN XY: 74386

African (AFR) AF: 0.223 AC: 9246 AN: 41502

American (AMR) AF: 0.326 AC: 4977 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1348 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2454 AN: 5174

South Asian (SAS) AF: 0.357 AC: 1723 AN: 4820

European-Finnish (FIN) AF: 0.268 AC: 2843 AN: 10592

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.273 AC: 18554 AN: 68002

Other (OTH) AF: 0.271 AC: 572 AN: 2114

Alfa AF: 0.264 Hom.: 844

Bravo AF: 0.278

Asia WGS AF: 0.411 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		0.31
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: rs4917772; hg19: chr10-99249505;