chr1-37815302-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_005955.3(MTF1):c.2096G>A(p.Arg699Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,613,930 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: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
MTF1
NM_005955.3 missense
NM_005955.3 missense
Scores
1
1
16
Clinical Significance
Conservation
PhyloP100: 3.66
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]
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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=0.06733033).
BS2
?
High AC in GnomAdExome at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTF1 | NM_005955.3 | c.2096G>A | p.Arg699Gln | missense_variant | 11/11 | ENST00000373036.5 | |
MTF1 | XM_011541491.3 | c.2096G>A | p.Arg699Gln | missense_variant | 11/11 | ||
MTF1 | XM_047421170.1 | c.2096G>A | p.Arg699Gln | missense_variant | 12/12 | ||
MTF1 | XM_047421173.1 | c.1169G>A | p.Arg390Gln | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTF1 | ENST00000373036.5 | c.2096G>A | p.Arg699Gln | missense_variant | 11/11 | 1 | NM_005955.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152044Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251300Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135854
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GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 727248
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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 | Apr 12, 2022 | The c.2096G>A (p.R699Q) alteration is located in exon 11 (coding exon 10) of the MTF1 gene. This alteration results from a G to A substitution at nucleotide position 2096, causing the arginine (R) at amino acid position 699 to be replaced by a glutamine (Q). 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
Uncertain
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 S698 (P = 0.1108);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at