rs3381

Variant names:

• chr10-97481381-C-T
• rs3381
• NM_022362.5:c.162-339G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022362.5(MMS19):​c.162-339G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 152,228 control chromosomes in the GnomAD database, including 85 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 0.028 (85 hom., cov: 32)
• Consequence: MMS19 NM_022362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• Publications: 6 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=-0.68).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0283 (4310/152228) while in subpopulation NFE AF = 0.0455 (3098/68022). AF 95% confidence interval is 0.0442. There are 85 homozygotes in GnomAd4. There are 2052 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4310 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMS19	NM_022362.5	c.162-339G>A		intron_variant	Intron 2 of 30	ENST00000438925.7	NP_071757.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMS19	ENST00000438925.7	c.162-339G>A		intron_variant	Intron 2 of 30	1	NM_022362.5	ENSP00000412698.2

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4310 AN: 152110 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.00758

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0211

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

GnomAD4 genome AF: 0.0283 AC: 4310 AN: 152228 Hom.: 85 Cov.: 32 AF XY: 0.0276 AC XY: 2052 AN XY: 74422

African (AFR) AF: 0.00758 AC: 315 AN: 41536

American (AMR) AF: 0.0225 AC: 344 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4816

European-Finnish (FIN) AF: 0.0335 AC: 355 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0455 AC: 3098 AN: 68022

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0349 Hom.: 14

Bravo AF: 0.0261

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.62
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3381; hg19: chr10-99241138;