16-56617689-C-T

Variant names:

• chr16-56617689-C-T
• rs904773
• ENST00000565768.4:n.315+99C>T

Variant summary

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

The ENST00000849449.1(ENSG00000291105):​n.86C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000377 in 265,278 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: ENSG00000291105 ENST00000849449.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 10 publications found

Genes affected

ENSG00000291105 (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

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=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000849449.1. 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
	MT1L	NR_001447.2		n.130+99C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000291105	ENST00000565768.4	TSL:1	n.315+99C>T		intron	N/A
	ENSG00000291105	ENST00000849449.1		n.86C>T		non_coding_transcript_exon	Exon 1 of 3
	MT1L	ENST00000566367.2	TSL:6	n.28+99C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000377 AC: 1 AN: 265278 Hom.: 0 AF XY: 0.00000659 AC XY: 1 AN XY: 151730

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7048

American (AMR) AF: 0.00 AC: 0 AN: 22564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5626

East Asian (EAS) AF: 0.00 AC: 0 AN: 11478

South Asian (SAS) AF: 0.00 AC: 0 AN: 48746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1074

European-Non Finnish (NFE) AF: 0.00000708 AC: 1 AN: 141236

Other (OTH) AF: 0.00 AC: 0 AN: 12038

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.49
DANN	Benign	0.94
PhyloP100		-2.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs904773;

hg19: chr16-56651601;