Variant 10-97460966-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000438925.7(MMS19):c.2353G>A(p.Val785Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,422,610 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

MMS19
ENST00000438925.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13132682).

BS2

High AC in GnomAdExome4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMS19	NM_022362.5 linkuse as main transcript	c.2353G>A	p.Val785Met	missense_variant	24/31	ENST00000438925.7	NP_071757.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMS19	ENST00000438925.7 linkuse as main transcript	c.2353G>A	p.Val785Met	missense_variant	24/31	1	NM_022362.5	ENSP00000412698	P1	Q96T76-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000208

AC:

AN:

192238

Hom.:

AF XY:

0.00000981

AC XY:

AN XY:

101962

show subpopulations

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 SAS exome

AF:

0.0000408

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000246

Gnomad OTH exome

AF:

0.000196

GnomAD4 exome

AF:

0.0000232

AC:

AN:

1422610

Hom.:

Cov.:

AF XY:

0.0000256

AC XY:

AN XY:

703790

show subpopulations

Gnomad4 AFR exome

AF:

0.000428

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000733

Gnomad4 OTH exome

AF:

0.000136

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000719

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000833

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

Jul 21, 2021

The c.2353G>A (p.V785M) alteration is located in exon 24 (coding exon 24) of the MMS19 gene. This alteration results from a G to A substitution at nucleotide position 2353, causing the valine (V) at amino acid position 785 to be replaced by a methionine (M). 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

0.14

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0031

T;T;.;.

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.87

.;D;D;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.2

L;L;.;.

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.38

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.060

B;B;D;.

Vest4

0.10

MutPred

0.36

Gain of disorder (P = 0.0967);Gain of disorder (P = 0.0967);.;.;

MVP

0.57

MPC

0.14

ClinPred

0.090

GERP RS

5.7

Varity_R

0.053

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

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