16-56652597-T-A

Variant names:

• chr16-56652597-T-A
• NM_005947.3:c.55T>A
• MT1B p.Cys19Ser

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_005947.3(MT1B):​c.55T>A​(p.Cys19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict 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)
• Consequence: MT1B NM_005947.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

Genes affected

MT1B (HGNC:7394): (metallothionein 1B) The protein encoded by this gene binds heavy metals and protects against toxicity from heavy metal ions. This gene is found in a cluster of similar genes on chromosome 16. [provided by RefSeq, Jul 2016]

ENSG00000259923 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity MT1B_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005947.3. 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
	MT1B	NM_005947.3	MANE Select	c.55T>A	p.Cys19Ser	missense	Exon 2 of 3	NP_005938.1	P07438

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1B	ENST00000334346.3	TSL:1 MANE Select	c.55T>A	p.Cys19Ser	missense	Exon 2 of 3	ENSP00000334998.2	P07438
	MT1B	ENST00000562399.1	TSL:3	c.55T>A	p.Cys19Ser	missense	Exon 2 of 3	ENSP00000456056.1	H3BR34
	ENSG00000259923	ENST00000568608.1	TSL:5	n.205T>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.82
DEOGEN2	Benign	0.36	T
Eigen	Benign	0.14
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.79	T
PhyloP100		2.3
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-9.3	D
REVEL	Benign	0.24
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.019	D
Varity_R		0.75
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

hg19: chr16-56686509;