Genetic Variant MT1E:c.*173G>T (chr16-56626994-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001363555.2(MT1E):c.*173G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,590 control chromosomes in the GnomAD database, including 13,947 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 0.14 ( 1499 hom., cov: 33)

Exomes 𝑓: 0.13 ( 12448 hom. )

Consequence

MT1E
NM_001363555.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

26 publications found

Variant links:

Genes affected

MT1E (HGNC:7397): (metallothionein 1E) Predicted to enable zinc ion binding activity. Involved in cellular response to cadmium ion and cellular response to zinc ion. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT1E links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1E	NM_001363555.2 link	c.*173G>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000330439.7	NP_001350484.1
MT1E	NM_175617.4 link	c.*23G>T		3_prime_UTR_variant	Exon 3 of 3		NP_783316.2	P04732-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MT1E	ENST00000330439.7 link	c.*173G>T	3_prime_UTR_variant	Exon 2 of 2	1	NM_001363555.2	ENSP00000328137.6	P04732-2
MT1E	ENST00000306061.10 link	c.*23G>T	3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000307706.5	P04732-1
MT1E	ENST00000568293.1 link	c.*23G>T	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000457516.1	H3BU80

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21147

AN:

152068

Hom.:

1495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.123

GnomAD2 exomes

AF:

0.141

AC:

35431

AN:

250716

AF XY:

0.140

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.128

AC:

186822

AN:

1461404

Hom.:

12448

Cov.:

AF XY:

0.128

AC XY:

93249

AN XY:

726998

show subpopulations

African (AFR)

AF:

0.159

AC:

5325

AN:

33456

American (AMR)

AF:

0.152

AC:

6776

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

2836

AN:

26122

East Asian (EAS)

AF:

0.226

AC:

8981

AN:

39694

South Asian (SAS)

AF:

0.160

AC:

13790

AN:

86204

European-Finnish (FIN)

AF:

0.119

AC:

6363

AN:

53410

Middle Eastern (MID)

AF:

0.108

AC:

623

AN:

5764

European-Non Finnish (NFE)

AF:

0.120

AC:

133875

AN:

1111760

Other (OTH)

AF:

0.137

AC:

8253

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

9667

19334

29001

38668

48335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5012

10024

15036

20048

25060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.139

AC:

21160

AN:

152186

Hom.:

1499

Cov.:

AF XY:

0.142

AC XY:

10530

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.158

AC:

6547

AN:

41498

American (AMR)

AF:

0.135

AC:

2062

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

368

AN:

3472

East Asian (EAS)

AF:

0.245

AC:

1269

AN:

5178

South Asian (SAS)

AF:

0.174

AC:

838

AN:

4828

European-Finnish (FIN)

AF:

0.127

AC:

1345

AN:

10598

Middle Eastern (MID)

AF:

0.0959

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.120

AC:

8193

AN:

68004

Other (OTH)

AF:

0.128

AC:

270

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

963

1925

2888

3850

4813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.119

Hom.:

870

Bravo

AF:

0.140

Asia WGS

AF:

0.198

AC:

687

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.2

(source)

DANN

Benign

0.76

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over