chr10-97498058-T-G

Variant names:

• chr10-97498058-T-G
• rs7915501
• NM_022362.5:c.112+215A>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.112+215A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,196 control chromosomes in the GnomAD database, including 4,579 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 0.24 (4579 hom., cov: 33)
• Consequence: MMS19 NM_022362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.946
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMS19	NM_022362.5	c.112+215A>C		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.112+215A>C		intron_variant	Intron 1 of 30	1	NM_022362.5	ENSP00000412698.2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35984 AN: 152078 Hom.: 4566 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.237 AC: 36031 AN: 152196 Hom.: 4579 Cov.: 33 AF XY: 0.241 AC XY: 17933 AN XY: 74430

African (AFR) AF: 0.223 AC: 9252 AN: 41544

American (AMR) AF: 0.262 AC: 4001 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3472

East Asian (EAS) AF: 0.501 AC: 2590 AN: 5174

South Asian (SAS) AF: 0.396 AC: 1909 AN: 4822

European-Finnish (FIN) AF: 0.201 AC: 2128 AN: 10602

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14279 AN: 67968

Other (OTH) AF: 0.229 AC: 484 AN: 2116

Alfa AF: 0.219 Hom.: 11801

Bravo AF: 0.236

Asia WGS AF: 0.436 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.3
DANN	Benign	0.55
PhyloP100		0.95
PromoterAI		0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7915501; hg19: chr10-99257815;