rs534357571

Variant names:

• chr1-37815426-G-C
• rs534357571
• NM_005955.3:c.1972C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-37815426-G-C
• chr1-37815426-G-A
• chr1-37815426-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 16/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74
• Publications: 1 publications found

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]

MTF1 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007999092).
• BS2: High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005955.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTF1	NM_005955.3	MANE Select	c.1972C>G	p.Pro658Ala	missense	Exon 11 of 11	NP_005946.2	Q14872

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTF1	ENST00000373036.5	TSL:1 MANE Select	c.1972C>G	p.Pro658Ala	missense	Exon 11 of 11	ENSP00000362127.3	Q14872
	MTF1	ENST00000880496.1		c.1972C>G	p.Pro658Ala	missense	Exon 10 of 10	ENSP00000550555.1
	MTF1	ENST00000880495.1		c.1969C>G	p.Pro657Ala	missense	Exon 11 of 11	ENSP00000550554.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000201 AC: 50 AN: 249176 AF XY: 0.000267

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000446

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000134 AC: 196 AN: 1460506 Hom.: 2 Cov.: 31 AF XY: 0.000153 AC XY: 111 AN XY: 726402

African (AFR) AF: 0.0000599 AC: 2 AN: 33380

American (AMR) AF: 0.0000673 AC: 3 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39680

South Asian (SAS) AF: 0.00117 AC: 101 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000702 AC: 78 AN: 1111184

Other (OTH) AF: 0.000149 AC: 9 AN: 60318

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74434

African (AFR) AF: 0.0000241 AC: 1 AN: 41546

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.000206 AC: 25

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.55
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.11
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.0080	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.7
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.12
Sift	Benign	0.42	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.21		Loss of glycosylation at P658 (P = 8e-04)
MVP		0.20
MPC		0.19
ClinPred		0.023	T
GERP RS		5.0
Varity_R		0.074
gMVP		0.070
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs534357571; hg19: chr1-38281098;