1-34988715-C-T

Variant names:

• chr1-34988715-C-T
• NM_007167.4:c.2367G>A
• ZMYM6 p.Leu789Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007167.4(ZMYM6):​c.2367G>A​(p.Leu789Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L789L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZMYM6 NM_007167.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.219 with no splicing effect.

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.2367G>A	p.Leu789Leu	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.2367G>A	p.Leu789Leu	synonymous	Exon 16 of 16	ENSP00000349708.4	O95789-3
	ZMYM6	ENST00000493328.5	TSL:1	n.3691G>A		non_coding_transcript_exon	Exon 15 of 15
	ENSG00000271741	ENST00000487874.1	TSL:5	n.2146+3519G>A		intron	N/A	ENSP00000421752.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.5
DANN	Benign	0.75
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-35454316;