rs1640593025

Variant names:

• chr1-34987289-G-C
• rs1640593025
• NM_007167.4:c.3793C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007167.4(ZMYM6):​c.3793C>G​(p.Pro1265Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZMYM6 NM_007167.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61

Genes affected

ZMYM6 (HGNC:13050): (zinc finger MYM-type containing 6) Predicted to enable DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000271741 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM6	NM_007167.4	c.3793C>G	p.Pro1265Ala	missense_variant	Exon 16 of 16	ENST00000357182.9	NP_009098.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYM6	ENST00000357182.9	c.3793C>G	p.Pro1265Ala	missense_variant	Exon 16 of 16	1	NM_007167.4	ENSP00000349708.4
ZMYM6	ENST00000493328.5	n.5117C>G		non_coding_transcript_exon_variant	Exon 15 of 15	1
ENSG00000271741	ENST00000487874.1	n.2147-3342C>G		intron_variant	Intron 15 of 16	5		ENSP00000421752.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3793C>G (p.P1265A) alteration is located in exon 16 (coding exon 15) of the ZMYM6 gene. This alteration results from a C to G substitution at nucleotide position 3793, causing the proline (P) at amino acid position 1265 to be replaced by an alanine (A). 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	0.15
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.32
Sift	Benign	0.069	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.57
MutPred		0.67		Loss of methylation at K1261 (P = 0.0554);
MVP		0.61
MPC		0.70
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.17
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs1640593025; hg19: chr1-35452890;