NM_022362.5:c.203C>G

Variant names:

• chr10-97481001-G-C
• rs2275586
• NM_022362.5:c.203C>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.203C>G​(p.Ala68Gly) variant causes a missense change. The variant allele was found at a frequency of 0.971 in 1,609,774 control chromosomes in the GnomAD database, including 760,040 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.95 (68667 hom., cov: 31)
  • Exomes 𝑓: 0.97 (691373 hom.)
• Consequence: MMS19 NM_022362.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82
• Publications: 31 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 (MetaRNN=5.7795955E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022362.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMS19	NM_022362.5	MANE Select	c.203C>G	p.Ala68Gly	missense	Exon 3 of 31	NP_071757.4
	MMS19	NM_001351356.2		c.203C>G	p.Ala68Gly	missense	Exon 3 of 32	NP_001338285.1
	MMS19	NM_001289405.2		c.203C>G	p.Ala68Gly	missense	Exon 4 of 32	NP_001276334.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMS19	ENST00000438925.7	TSL:1 MANE Select	c.203C>G	p.Ala68Gly	missense	Exon 3 of 31	ENSP00000412698.2
	MMS19	ENST00000370782.6	TSL:1	c.203C>G	p.Ala68Gly	missense	Exon 4 of 32	ENSP00000359818.1
	MMS19	ENST00000355839.10	TSL:1	c.203C>G	p.Ala68Gly	missense	Exon 3 of 30	ENSP00000348097.6

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144358 AN: 152136 Hom.: 68622 Cov.: 31

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.979

Gnomad OTH AF: 0.962

GnomAD2 exomes AF: 0.967 AC: 237475 AN: 245628 AF XY: 0.967

Gnomad AFR exome AF: 0.887

Gnomad AMR exome AF: 0.988

Gnomad ASJ exome AF: 0.978

Gnomad EAS exome AF: 0.977

Gnomad FIN exome AF: 0.960

Gnomad NFE exome AF: 0.980

Gnomad OTH exome AF: 0.973

GnomAD4 exome AF: 0.974 AC: 1419255 AN: 1457520 Hom.: 691373 Cov.: 40 AF XY: 0.973 AC XY: 705102 AN XY: 724616

African (AFR) AF: 0.880 AC: 29400 AN: 33408

American (AMR) AF: 0.987 AC: 43630 AN: 44218

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 25447 AN: 26022

East Asian (EAS) AF: 0.956 AC: 37886 AN: 39624

South Asian (SAS) AF: 0.932 AC: 79330 AN: 85130

European-Finnish (FIN) AF: 0.962 AC: 51248 AN: 53254

Middle Eastern (MID) AF: 0.969 AC: 5554 AN: 5734

European-Non Finnish (NFE) AF: 0.981 AC: 1088255 AN: 1109886

Other (OTH) AF: 0.971 AC: 58505 AN: 60244

GnomAD4 genome AF: 0.949 AC: 144462 AN: 152254 Hom.: 68667 Cov.: 31 AF XY: 0.949 AC XY: 70633 AN XY: 74442

African (AFR) AF: 0.883 AC: 36653 AN: 41504

American (AMR) AF: 0.977 AC: 14947 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.974 AC: 3383 AN: 3472

East Asian (EAS) AF: 0.969 AC: 5018 AN: 5178

South Asian (SAS) AF: 0.931 AC: 4494 AN: 4826

European-Finnish (FIN) AF: 0.955 AC: 10137 AN: 10616

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.979 AC: 66642 AN: 68040

Other (OTH) AF: 0.962 AC: 2030 AN: 2110

Alfa AF: 0.973 Hom.: 23357

Bravo AF: 0.949

TwinsUK AF: 0.982 AC: 3642

ALSPAC AF: 0.980 AC: 3777

ESP6500AA AF: 0.885 AC: 3901

ESP6500EA AF: 0.978 AC: 8411

ExAC AF: 0.964 AC: 116953

Asia WGS AF: 0.951 AC: 3305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.036
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.69
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	5.8e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.52	N
PhyloP100		3.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	3.7	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.089
MPC		0.13
ClinPred		0.011	T
GERP RS		6.1
Varity_R		0.078
gMVP		0.45
Mutation Taster		=281/19	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs2275586; hg19: chr10-99240758; COSMIC: COSV107378657;