NM_007167.4:c.2568T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

ZMYM6 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, G2P

ENSG00000271741 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007167.4. 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
	ZMYM6	NM_007167.4	MANE Select	c.2568T>C	p.Tyr856Tyr	synonymous	Exon 16 of 16	NP_009098.3	O95789-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM6	ENST00000357182.9	TSL:1 MANE Select	c.2568T>C	p.Tyr856Tyr	synonymous	Exon 16 of 16	ENSP00000349708.4	O95789-3
	ZMYM6	ENST00000493328.5	TSL:1	n.3892T>C		non_coding_transcript_exon	Exon 15 of 15
	ENSG00000271741	ENST00000487874.1	TSL:5	n.2146+3720T>C		intron	N/A	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

GnomAD2 exomes AF: 0.00952 AC: 1435 AN: 150756 AF XY: 0.00759

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 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

African (AFR) AF: 0.137 AC: 4325 AN: 31578

American (AMR) AF: 0.00837 AC: 298 AN: 35594

Ashkenazi Jewish (ASJ) AF: 0.0174 AC: 437 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 35710

South Asian (SAS) AF: 0.000393 AC: 31 AN: 78942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49220

Middle Eastern (MID) AF: 0.00737 AC: 42 AN: 5696

European-Non Finnish (NFE) AF: 0.000367 AC: 396 AN: 1078722

Other (OTH) AF: 0.0117 AC: 676 AN: 57966

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

African (AFR) AF: 0.127 AC: 5292 AN: 41546

American (AMR) AF: 0.0135 AC: 207 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68028

Other (OTH) AF: 0.0279 AC: 59 AN: 2116

Alfa AF: 0.0181 Hom.: 97

Bravo AF: 0.0430

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ZMYM6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.3
DANN	Benign	0.81
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61745582; hg19: chr1-35454115;