rs17851637

chr16-56683202-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005952.4(MT1X):c.66A>C(p.Lys22Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K22E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MT1X NM_005952.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266

Genes affected

MT1X (HGNC:7405): (metallothionein 1X) Predicted to enable copper ion binding activity and zinc ion binding activity. Involved in cellular response to cadmium ion; cellular response to erythropoietin; and cellular response to zinc ion. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MT1X	NM_005952.4	c.66A>C	p.Lys22Asn	missense_variant	2/3	ENST00000394485.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT1X	ENST00000394485.5	c.66A>C	p.Lys22Asn	missense_variant	2/3	1	NM_005952.4	P1
MT1X	ENST00000562939.1	c.66A>C	p.Lys22Asn	missense_variant	2/2	1
MT1X	ENST00000564974.1	c.66A>C	p.Lys22Asn	missense_variant, NMD_transcript_variant	2/3	1
MT1X	ENST00000568370.1	n.733A>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-0.053
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.57	T;.
M_CAP	Benign	0.0044	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.55	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.1	D;.
REVEL	Benign	0.051
Sift	Uncertain	0.011	D;.
Sift4G	Benign	0.10	T;D
Polyphen		1.0	D;.
Vest4		0.56
MutPred		0.36		Loss of methylation at K22 (P = 0.0011);Loss of methylation at K22 (P = 0.0011);
MVP		0.50
MPC		0.36
ClinPred		0.94	D
GERP RS		1.6
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.42
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs17851637; hg19: chr16-56717114;