Genetic Variant ENST00000565768.4:n.315+99C>T (chr16-56617689-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000565768.4(ENSG00000291105):n.315+99C>T variant causes a intron 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
ENST00000565768.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.16

Publications

10 publications found

Variant links:

Genes affected

ENSG00000291105 (HGNC:):

ENSG00000291105 links:

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]

MT1L links:

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ACMG classification

Classification was made for transcript

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: ENST00000565768.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1L	NR_001447.2		n.130+99C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
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.:

GnomAD4 exome

AF:

0.00000377

AC:

AN:

265278

Hom.:

AF XY:

0.00000659

AC XY:

AN XY:

151730

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

7048

American (AMR)

AF:

0.00

AC:

AN:

22564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5626

East Asian (EAS)

AF:

0.00

AC:

AN:

11478

South Asian (SAS)

AF:

0.00

AC:

AN:

48746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1074

European-Non Finnish (NFE)

AF:

0.00000708

AC:

AN:

141236

Other (OTH)

AF:

0.00

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

(source)

DANN

Benign

0.94

PhyloP100

-2.2

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over