chr10-97459275-C-T

Variant names:

• chr10-97459275-C-T
• rs1358291193
• NM_022362.5:c.2912G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_Strong BS2

The NM_022362.5(MMS19):​c.2912G>A​(p.Arg971Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: MMS19 NM_022362.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.985
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMS19	NM_022362.5	MANE Select	c.2912G>A	p.Arg971Gln	missense	Exon 29 of 31	NP_071757.4
	MMS19	NM_001351356.2		c.3029G>A	p.Arg1010Gln	missense	Exon 30 of 32	NP_001338285.1
	MMS19	NM_001289405.2		c.2912G>A	p.Arg971Gln	missense	Exon 30 of 32	NP_001276334.1	Q96T76-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMS19	ENST00000438925.7	TSL:1 MANE Select	c.2912G>A	p.Arg971Gln	missense	Exon 29 of 31	ENSP00000412698.2	Q96T76-1
	MMS19	ENST00000370782.6	TSL:1	c.2912G>A	p.Arg971Gln	missense	Exon 30 of 32	ENSP00000359818.1	Q96T76-1
	MMS19	ENST00000355839.10	TSL:1	c.2783G>A	p.Arg928Gln	missense	Exon 28 of 30	ENSP00000348097.6	Q96T76-9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250100 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461026 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726732

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86136

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111526

Other (OTH) AF: 0.0000166 AC: 1 AN: 60340

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000301 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	T
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Pathogenic	3.5	H
PhyloP100		6.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.7	D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.90		Gain of catalytic residue at R971 (P = 0.0237)
MVP		0.90
MPC		0.64
ClinPred		1.0	D
GERP RS		5.9
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
gMVP		0.76
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1358291193; hg19: chr10-99219032;