rs904773

chr16-56617689-C-Achr16-56617689-C-Gchr16-56617689-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_001447.2(MT1L):n.130+99C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 416,980 control chromosomes in the GnomAD database, including 132,533 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 0.80 (49136 hom., cov: 33)
  • Exomes 𝑓: 0.79 (83397 hom.)
• Consequence: MT1L NR_001447.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

Genes affected

(HGNC:):

MT1L (HGNC:7404): (metallothionein 1L (pseudogene)) Predicted to enable zinc ion binding activity. Involved in cellular response to zinc ion. Predicted to be active 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MT1L	NR_001447.2	n.130+99C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000565768.3	n.168+99C>A		intron_variant, non_coding_transcript_variant		1
MT1L	ENST00000566367.2	n.28+99C>A		intron_variant, non_coding_transcript_variant
	ENST00000686205.1	n.146+99C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121955 AN: 152038 Hom.: 49095 Cov.: 33

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.847

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.792 AC: 209822 AN: 264826 Hom.: 83397 AF XY: 0.795 AC XY: 120339 AN XY: 151444

Gnomad4 AFR exome AF: 0.836

Gnomad4 AMR exome AF: 0.681

Gnomad4 ASJ exome AF: 0.803

Gnomad4 EAS exome AF: 0.760

Gnomad4 SAS exome AF: 0.807

Gnomad4 FIN exome AF: 0.743

Gnomad4 NFE exome AF: 0.809

Gnomad4 OTH exome AF: 0.802

GnomAD4 genome AF: 0.802 AC: 122049 AN: 152154 Hom.: 49136 Cov.: 33 AF XY: 0.798 AC XY: 59314 AN XY: 74368

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.806

Alfa AF: 0.809 Hom.: 12168

Bravo AF: 0.800

Asia WGS AF: 0.786 AC: 2731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.34
Dann	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs904773; hg19: chr16-56651601;