13-19837810-G-A

Variant names:

• chr13-19837810-G-A
• rs748200567
• ENST00000382907.8:c.598C>T

Variant summary

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

The NM_001039649.3(ZMYM5):​c.598C>T​(p.Gln200*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000418 in 1,435,620 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: ZMYM5 NM_001039649.3 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54

Genes affected

ZMYM5 (HGNC:13029): (zinc finger MYM-type containing 5) Predicted to enable zinc ion binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in 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 rank	MANE	Protein	UniProt
ZMYM5	NM_001142684.2	c.884C>T	p.Thr295Ile	missense_variant	Exon 6 of 8	ENST00000337963.9	NP_001136156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYM5	ENST00000337963.9	c.884C>T	p.Thr295Ile	missense_variant	Exon 6 of 8	5	NM_001142684.2	ENSP00000337034.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000221 AC: 5 AN: 225748 Hom.: 0 AF XY: 0.0000326 AC XY: 4 AN XY: 122628

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000300

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000418 AC: 6 AN: 1435620 Hom.: 0 Cov.: 31 AF XY: 0.00000420 AC XY: 3 AN XY: 713808

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000128

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.884C>T (p.T295I) alteration is located in exon 6 (coding exon 4) of the ZMYM5 gene. This alteration results from a C to T substitution at nucleotide position 884, causing the threonine (T) at amino acid position 295 to be replaced by an isoleucine (I). 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	0.12
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.91	D
Vest4		0.061
ClinPred		0.62	D
GERP RS		3.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs748200567; hg19: chr13-20411950;