rs372808832

Variant names:

• chr10-97459270-C-A
• NM_022362.5:c.2917G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-97459270-C-A
• chr10-97459270-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022362.5(MMS19):​c.2917G>T​(p.Ala973Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A973T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MMS19 NM_022362.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.70

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38517028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMS19	NM_022362.5	c.2917G>T	p.Ala973Ser	missense_variant	Exon 29 of 31	ENST00000438925.7	NP_071757.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMS19	ENST00000438925.7	c.2917G>T	p.Ala973Ser	missense_variant	Exon 29 of 31	1	NM_022362.5	ENSP00000412698.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460892 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726634

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0029	T;T;.;.
Eigen	Benign	-0.063
Eigen_PC	Benign	0.0047
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	.;T;T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.3	L;L;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.20
Sift	Uncertain	0.027	D;D;T;D
Sift4G	Uncertain	0.018	D;D;D;D
Polyphen		0.075	B;B;P;.
Vest4		0.39
MutPred		0.75		Gain of disorder (P = 0.0531);Gain of disorder (P = 0.0531);.;.;
MVP		0.63
MPC		0.13
ClinPred		0.62	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.091
gMVP		0.20

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-99219027;