chr16-56626994-G-T

Position:

• chr16-56626994-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MT1E	NM_001363555.2	c.*173G>T		3_prime_UTR_variant	2/2	ENST00000330439.7	NP_001350484.1
MT1E	NM_175617.4	c.*23G>T		3_prime_UTR_variant	3/3		NP_783316.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1E	ENST00000330439.7	c.*173G>T		3_prime_UTR_variant	2/2	1	NM_001363555.2	ENSP00000328137
MT1E	ENST00000306061.10	c.*23G>T		3_prime_UTR_variant	3/3	1		ENSP00000307706	P1
MT1E	ENST00000568293.1	c.*23G>T		3_prime_UTR_variant	2/2	2		ENSP00000457516

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

GnomAD3 exomes AF: 0.141 AC: 35431 AN: 250716 Hom.: 2625 AF XY: 0.140 AC XY: 18992 AN XY: 135484

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 SAS exome AF: 0.158

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

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.137

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

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.128

Alfa AF: 0.119 Hom.: 758

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
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs708274; hg19: chr16-56660906;