rs28378413

Variant names:

• chr1-37835548-G-A
• rs28378413
• NM_005955.3:c.853+123C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-37835548-G-A
• chr1-37835548-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005955.3(MTF1):​c.853+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 750,142 control chromosomes in the GnomAD database, including 26,079 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4115 hom., cov: 32)
  • Exomes 𝑓: 0.26 (21964 hom.)
• Consequence: MTF1 NM_005955.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTF1	NM_005955.3	MANE Select	c.853+123C>T		intron	N/A	NP_005946.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTF1	ENST00000373036.5	TSL:1 MANE Select	c.853+123C>T		intron	N/A	ENSP00000362127.3
	MTF1	ENST00000880496.1		c.853+123C>T		intron	N/A	ENSP00000550555.1
	MTF1	ENST00000880495.1		c.853+123C>T		intron	N/A	ENSP00000550554.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31496 AN: 151980 Hom.: 4109 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.264 AC: 158147 AN: 598042 Hom.: 21964 AF XY: 0.261 AC XY: 81848 AN XY: 313256

African (AFR) AF: 0.0496 AC: 744 AN: 14990

American (AMR) AF: 0.269 AC: 6350 AN: 23568

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 1894 AN: 16382

East Asian (EAS) AF: 0.222 AC: 7084 AN: 31884

South Asian (SAS) AF: 0.203 AC: 10856 AN: 53404

European-Finnish (FIN) AF: 0.330 AC: 14980 AN: 45356

Middle Eastern (MID) AF: 0.162 AC: 486 AN: 3000

European-Non Finnish (NFE) AF: 0.286 AC: 108288 AN: 378520

Other (OTH) AF: 0.241 AC: 7465 AN: 30938

GnomAD4 genome AF: 0.207 AC: 31508 AN: 152100 Hom.: 4115 Cov.: 32 AF XY: 0.209 AC XY: 15558 AN XY: 74348

African (AFR) AF: 0.0523 AC: 2170 AN: 41510

American (AMR) AF: 0.260 AC: 3967 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3472

East Asian (EAS) AF: 0.208 AC: 1077 AN: 5174

South Asian (SAS) AF: 0.202 AC: 971 AN: 4818

European-Finnish (FIN) AF: 0.332 AC: 3502 AN: 10564

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18785 AN: 67960

Other (OTH) AF: 0.195 AC: 411 AN: 2110

Alfa AF: 0.225 Hom.: 574

Bravo AF: 0.195

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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: rs28378413; hg19: chr1-38301220;