1-34988514-A-G

Variant names:

• chr1-34988514-A-G
• rs61745582
• NM_007167.4:c.2568T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_007167.4(ZMYM6):​c.2568T>C​(p.Tyr856Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00764 in 1,550,912 control chromosomes in the GnomAD database, including 660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.037 (337 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (323 hom.)
• Consequence: ZMYM6 NM_007167.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.600

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-34988514-A-G is Benign according to our data. Variant chr1-34988514-A-G is described in ClinVar as [Benign]. Clinvar id is 3037385.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM6	NM_007167.4	c.2568T>C	p.Tyr856Tyr	synonymous_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.2568T>C	p.Tyr856Tyr	synonymous_variant	Exon 16 of 16	1	NM_007167.4	ENSP00000349708.4
ZMYM6	ENST00000493328.5	n.3892T>C		non_coding_transcript_exon_variant	Exon 15 of 15	1
ENSG00000271741	ENST00000487874.1	n.2146+3720T>C		intron_variant	Intron 15 of 16	5		ENSP00000421752.1

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5617 AN: 152198 Hom.: 333 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0282

GnomAD3 exomes AF: 0.00952 AC: 1435 AN: 150756 Hom.: 81 AF XY: 0.00759 AC XY: 607 AN XY: 79960

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.00644

Gnomad ASJ exome AF: 0.0160

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000223

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000789

Gnomad OTH exome AF: 0.00814

GnomAD4 exome AF: 0.00444 AC: 6205 AN: 1398596 Hom.: 323 Cov.: 32 AF XY: 0.00392 AC XY: 2702 AN XY: 689676

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.00837

Gnomad4 ASJ exome AF: 0.0174

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000393

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000367

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.0371 AC: 5645 AN: 152316 Hom.: 337 Cov.: 33 AF XY: 0.0362 AC XY: 2697 AN XY: 74498

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0176 Hom.: 67

Bravo AF: 0.0430

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ZMYM6-related disorder Benign:1

Oct 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.3
DANN	Benign	0.81

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: rs61745582; hg19: chr1-35454115;