10-97481001-G-C

Position:

• chr10-97481001-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000438925.7(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. 12/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.95 (68667 hom., cov: 31)
  • Exomes 𝑓: 0.97 (691373 hom.)
• Consequence: MMS19 ENST00000438925.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMS19	NM_022362.5	c.203C>G	p.Ala68Gly	missense_variant	3/31	ENST00000438925.7	NP_071757.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMS19	ENST00000438925.7	c.203C>G	p.Ala68Gly	missense_variant	3/31	1	NM_022362.5	ENSP00000412698	P1

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

GnomAD3 exomes AF: 0.967 AC: 237475 AN: 245628 Hom.: 114874 AF XY: 0.967 AC XY: 128050 AN XY: 132466

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 SAS exome AF: 0.931

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

Gnomad4 AFR exome AF: 0.880

Gnomad4 AMR exome AF: 0.987

Gnomad4 ASJ exome AF: 0.978

Gnomad4 EAS exome AF: 0.956

Gnomad4 SAS exome AF: 0.932

Gnomad4 FIN exome AF: 0.962

Gnomad4 NFE exome AF: 0.981

Gnomad4 OTH exome AF: 0.971

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

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.977

Gnomad4 ASJ AF: 0.974

Gnomad4 EAS AF: 0.969

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.955

Gnomad4 NFE AF: 0.979

Gnomad4 OTH AF: 0.962

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 v4.3

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;T;.;.;T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.57	.;T;T;T;T;T
MetaRNN	Benign	5.8e-7	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.52	N;N;N;N;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	3.7	N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;.;.
Polyphen		0.0	B;B;.;.;.;.
Vest4		0.089
MPC		0.13
ClinPred		0.011	T
GERP RS		6.1
Varity_R		0.078
gMVP		0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs2275586; hg19: chr10-99240758;