chr1-37815426-G-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_005955.3(MTF1):c.1972C>G(p.Pro658Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,612,750 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 2 hom. )
Consequence
MTF1
NM_005955.3 missense
NM_005955.3 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 1.74
Genes affected
MTF1 (HGNC:7428): (metal regulatory transcription factor 1) This gene encodes a transcription factor that induces expression of metallothioneins and other genes involved in metal homeostasis in response to heavy metals such as cadmium, zinc, copper, and silver. The protein is a nucleocytoplasmic shuttling protein that accumulates in the nucleus upon heavy metal exposure and binds to promoters containing a metal-responsive element (MRE). [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, MTF1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.007999092).
BS2
?
High AC in GnomAd at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTF1 | NM_005955.3 | c.1972C>G | p.Pro658Ala | missense_variant | 11/11 | ENST00000373036.5 | |
MTF1 | XM_011541491.3 | c.1972C>G | p.Pro658Ala | missense_variant | 11/11 | ||
MTF1 | XM_047421170.1 | c.1972C>G | p.Pro658Ala | missense_variant | 12/12 | ||
MTF1 | XM_047421173.1 | c.1045C>G | p.Pro349Ala | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTF1 | ENST00000373036.5 | c.1972C>G | p.Pro658Ala | missense_variant | 11/11 | 1 | NM_005955.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152126Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
11
AN:
152126
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000201 AC: 50AN: 249176Hom.: 1 AF XY: 0.000267 AC XY: 36AN XY: 134840
GnomAD3 exomes
AF:
AC:
50
AN:
249176
Hom.:
AF XY:
AC XY:
36
AN XY:
134840
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000134 AC: 196AN: 1460506Hom.: 2 Cov.: 31 AF XY: 0.000153 AC XY: 111AN XY: 726402
GnomAD4 exome
AF:
AC:
196
AN:
1460506
Hom.:
Cov.:
31
AF XY:
AC XY:
111
AN XY:
726402
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74434
GnomAD4 genome
?
AF:
AC:
11
AN:
152244
Hom.:
Cov.:
32
AF XY:
AC XY:
7
AN XY:
74434
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
25
Asia WGS
AF:
AC:
3
AN:
3478
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 04, 2022 | The c.1972C>G (p.P658A) alteration is located in exon 11 (coding exon 10) of the MTF1 gene. This alteration results from a C to G substitution at nucleotide position 1972, causing the proline (P) at amino acid position 658 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of glycosylation at P658 (P = 8e-04);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at