rs708274

Variant names:

• chr16-56626994-G-T
• rs708274
• NM_001363555.2:c.*173G>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 26 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363555.2. 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
	MT1E	NM_001363555.2	MANE Select	c.*173G>T		3_prime_UTR	Exon 2 of 2	NP_001350484.1	P04732-2
	MT1E	NM_175617.4		c.*23G>T		3_prime_UTR	Exon 3 of 3	NP_783316.2	P04732-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1E	ENST00000330439.7	TSL:1 MANE Select	c.*173G>T		3_prime_UTR	Exon 2 of 2	ENSP00000328137.6	P04732-2
	MT1E	ENST00000306061.10	TSL:1	c.*23G>T		3_prime_UTR	Exon 3 of 3	ENSP00000307706.5	P04732-1
	MT1E	ENST00000568293.1	TSL:2	c.*23G>T		3_prime_UTR	Exon 2 of 2	ENSP00000457516.1	H3BU80

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21147 AN: 152068 Hom.: 1495 Cov.: 33

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

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.: 33 AF XY: 0.128 AC XY: 93249 AN XY: 726998

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

GnomAD4 genome AF: 0.139 AC: 21160 AN: 152186 Hom.: 1499 Cov.: 33 AF XY: 0.142 AC XY: 10530 AN XY: 74416

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: 28 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8193 AN: 68004

Other (OTH) AF: 0.128 AC: 270 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
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)

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: rs708274; hg19: chr16-56660906;