Variant 10-97462069-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_022362.5(MMS19):c.2063A>G(p.Asn688Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000322 in 1,592,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

MMS19
NM_022362.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.18

Variant links:

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]

MMS19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMS19	NM_022362.5 linkuse as main transcript	c.2063A>G	p.Asn688Ser	missense_variant	21/31	ENST00000438925.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMS19	ENST00000438925.7 linkuse as main transcript	c.2063A>G	p.Asn688Ser	missense_variant	21/31	1	NM_022362.5	P1	Q96T76-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000198

AC:

AN:

216942

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

115926

show subpopulations

Gnomad AFR exome

AF:

0.0000749

Gnomad AMR exome

AF:

0.000130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000370

Gnomad SAS exome

AF:

0.000422

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000198

Gnomad OTH exome

AF:

0.000360

GnomAD4 exome

AF:

0.000338

AC:

486

AN:

1439712

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

240

AN XY:

713844

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000121

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000155

Gnomad4 SAS exome

AF:

0.000425

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.000386

Gnomad4 OTH exome

AF:

0.000235

GnomAD4 genome

AF:

0.000171

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000173

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2022

The c.2063A>G (p.N688S) alteration is located in exon 21 (coding exon 21) of the MMS19 gene. This alteration results from a A to G substitution at nucleotide position 2063, causing the asparagine (N) at amino acid position 688 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.45

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0025

T;T;.;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.025

MetaRNN

Benign

0.072

T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.4

L;L;.;.

MutationTaster

Benign

0.92

D;D;D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.036

D;D;D;D

Sift4G

Uncertain

0.034

D;D;D;D

Polyphen

0.046

B;B;P;.

Vest4

0.13

MVP

0.62

MPC

0.11

ClinPred

0.048

GERP RS

5.8

Varity_R

0.13

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over