1-37835548-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005955.3(MTF1):​c.853+123C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTF1	NM_005955.3	c.853+123C>A		intron_variant	Intron 5 of 10	ENST00000373036.5	NP_005946.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTF1	ENST00000373036.5	c.853+123C>A		intron_variant	Intron 5 of 10	1	NM_005955.3	ENSP00000362127.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 599030 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 313752

African (AFR) AF: 0.00 AC: 0 AN: 14990

American (AMR) AF: 0.00 AC: 0 AN: 23590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16398

East Asian (EAS) AF: 0.00 AC: 0 AN: 31902

South Asian (SAS) AF: 0.00 AC: 0 AN: 53476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3002

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 379274

Other (OTH) AF: 0.00 AC: 0 AN: 30970

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		-0.10

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;