1-34988050-A-C

Variant names:

• chr1-34988050-A-C
• rs61744853
• NM_007167.4:c.3032T>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_007167.4(ZMYM6):​c.3032T>G​(p.Phe1011Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00659 in 1,551,608 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0069 (49 hom.)
• Consequence: ZMYM6 NM_007167.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.23
• Publications: 9 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011003286).
• BP6: Variant 1-34988050-A-C is Benign according to our data. Variant chr1-34988050-A-C is described in ClinVar as Benign. ClinVar VariationId is 3035215.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 589 AD gene.

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.3032T>G	p.Phe1011Cys	missense	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.3032T>G	p.Phe1011Cys	missense	Exon 16 of 16	ENSP00000349708.4	O95789-3
	ZMYM6	ENST00000493328.5	TSL:1	n.4356T>G		non_coding_transcript_exon	Exon 15 of 15
	ENSG00000271741	ENST00000487874.1	TSL:5	n.2147-4103T>G		intron	N/A	ENSP00000421752.1

Frequencies

GnomAD3 genomes AF: 0.00387 AC: 589 AN: 152246 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00669

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00341 AC: 517 AN: 151628 AF XY: 0.00339

Gnomad AFR exome AF: 0.000890

Gnomad AMR exome AF: 0.00300

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00144

Gnomad NFE exome AF: 0.00678

Gnomad OTH exome AF: 0.00556

GnomAD4 exome AF: 0.00688 AC: 9633 AN: 1399244 Hom.: 49 Cov.: 32 AF XY: 0.00680 AC XY: 4690 AN XY: 690116

African (AFR) AF: 0.000981 AC: 31 AN: 31598

American (AMR) AF: 0.00375 AC: 134 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.0000794 AC: 2 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35726

South Asian (SAS) AF: 0.0000757 AC: 6 AN: 79214

European-Finnish (FIN) AF: 0.00140 AC: 69 AN: 49196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00840 AC: 9064 AN: 1078940

Other (OTH) AF: 0.00564 AC: 327 AN: 57992

GnomAD4 genome AF: 0.00387 AC: 589 AN: 152364 Hom.: 0 Cov.: 33 AF XY: 0.00337 AC XY: 251 AN XY: 74510

African (AFR) AF: 0.00168 AC: 70 AN: 41586

American (AMR) AF: 0.00281 AC: 43 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00669 AC: 455 AN: 68038

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00561 Hom.: 4

Bravo AF: 0.00442

TwinsUK AF: 0.0105 AC: 39

ALSPAC AF: 0.0106 AC: 41

ExAC AF: 0.00184 AC: 41

Asia WGS AF: 0.000289 AC: 2 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
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.61
MVP		0.27
MPC		0.79
ClinPred		0.044	T
GERP RS		4.7
Varity_R		0.23
gMVP		0.55
Mutation Taster		=92/8	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

Other links and lift over

dbSNP: rs61744853; hg19: chr1-35453651; COSMIC: COSV100593399; COSMIC: COSV100593399;