1-35110296-A-T

Variant names:

• chr1-35110296-A-T
• NM_024772.5:c.810A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024772.5(ZMYM1):​c.810A>T​(p.Lys270Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,359,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ZMYM1 NM_024772.5 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23

Genes affected

ZMYM1 (HGNC:26253): (zinc finger MYM-type containing 1) Predicted to enable protein dimerization activity and zinc ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14259857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM1	NM_024772.5	c.810A>T	p.Lys270Asn	missense_variant, splice_region_variant	Exon 7 of 10	ENST00000359858.9	NP_079048.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYM1	ENST00000359858.9	c.810A>T	p.Lys270Asn	missense_variant, splice_region_variant	Exon 7 of 10	1	NM_024772.5	ENSP00000352920.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1359700 Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1 AN XY: 674702

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.810A>T (p.K270N) alteration is located in exon 7 (coding exon 6) of the ZMYM1 gene. This alteration results from a A to T substitution at nucleotide position 810, causing the lysine (K) at amino acid position 270 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0018	T;.;T;T;T
Eigen	Benign	0.072
Eigen_PC	Benign	0.087
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.80	.;T;T;.;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;L;L;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	.;N;.;N;N
REVEL	Benign	0.037
Sift	Benign	0.21	.;T;.;D;D
Sift4G	Benign	0.62	.;T;T;T;T
Polyphen		1.0	D;.;D;D;D
Vest4		0.56, 0.55, 0.56
MutPred		0.35		Loss of MoRF binding (P = 0.0826);Loss of MoRF binding (P = 0.0826);Loss of MoRF binding (P = 0.0826);Loss of MoRF binding (P = 0.0826);Loss of MoRF binding (P = 0.0826);
MVP		0.28
MPC		0.70
ClinPred		0.74	D
GERP RS		3.1
Varity_R		0.28
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-35575897;