rs17851637

Variant names:

• chr16-56683202-A-C
• rs17851637
• NM_005952.4:c.66A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 1 publications found

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]

ENSG00000259827 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005952.4. 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
	MT1X	NM_005952.4	MANE Select	c.66A>C	p.Lys22Asn	missense	Exon 2 of 3	NP_005943.1	A0A140VJP8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1X	ENST00000394485.5	TSL:1 MANE Select	c.66A>C	p.Lys22Asn	missense	Exon 2 of 3	ENSP00000377995.4	P80297
	MT1X	ENST00000562939.1	TSL:1	c.66A>C	p.Lys22Asn	missense	Exon 2 of 2	ENSP00000475791.1	U3KQD7
	MT1X	ENST00000564974.1	TSL:1	n.66A>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000475537.1	U3KQD7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.0	T
PhyloP100		0.27
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.051
Sift	Uncertain	0.011	D
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.36		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

Other links and lift over

dbSNP: rs17851637; hg19: chr16-56717114;