rs141138840

Variant names:

• chr1-34988276-G-A
• rs141138840
• NM_007167.4:c.2806C>T

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.2806C>T​(p.Arg936Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00078 in 1,550,370 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0035 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (2 hom.)
• Consequence: ZMYM6 NM_007167.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.220
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039242506).
• BP6: Variant 1-34988276-G-A is Benign according to our data. Variant chr1-34988276-G-A is described in ClinVar as Benign. ClinVar VariationId is 3041852.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 536 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.2806C>T	p.Arg936Cys	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.2806C>T	p.Arg936Cys	missense	Exon 16 of 16	ENSP00000349708.4	O95789-3
	ZMYM6	ENST00000493328.5	TSL:1	n.4130C>T		non_coding_transcript_exon	Exon 15 of 15
	ENSG00000271741	ENST00000487874.1	TSL:5	n.2146+3958C>T		intron	N/A	ENSP00000421752.1

Frequencies

GnomAD3 genomes AF: 0.00343 AC: 522 AN: 152064 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00108 AC: 163 AN: 151106 AF XY: 0.000836

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.000732

Gnomad ASJ exome AF: 0.00424

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000876

Gnomad OTH exome AF: 0.000464

GnomAD4 exome AF: 0.000481 AC: 673 AN: 1398188 Hom.: 2 Cov.: 32 AF XY: 0.000421 AC XY: 290 AN XY: 689386

African (AFR) AF: 0.0124 AC: 391 AN: 31592

American (AMR) AF: 0.000897 AC: 32 AN: 35666

Ashkenazi Jewish (ASJ) AF: 0.00294 AC: 74 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 35708

South Asian (SAS) AF: 0.000127 AC: 10 AN: 78996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49102

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5696

European-Non Finnish (NFE) AF: 0.0000677 AC: 73 AN: 1078294

Other (OTH) AF: 0.00155 AC: 90 AN: 57968

GnomAD4 genome AF: 0.00352 AC: 536 AN: 152182 Hom.: 6 Cov.: 33 AF XY: 0.00350 AC XY: 260 AN XY: 74388

African (AFR) AF: 0.0117 AC: 485 AN: 41524

American (AMR) AF: 0.00164 AC: 25 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67988

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00219 Hom.: 0

Bravo AF: 0.00397

ESP6500AA AF: 0.00688 AC: 16

ESP6500EA AF: 0.000606 AC: 3

ExAC AF: 0.00127 AC: 28

Asia WGS AF: 0.000866 AC: 3 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	0.088
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.78
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.49	N
PhyloP100		-0.22
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.025
Sift	Benign	0.042	D
Sift4G	Uncertain	0.022	D
Polyphen		0.40	B
Vest4		0.075
MVP		0.040
MPC		0.52
ClinPred		0.013	T
GERP RS		-2.2
Varity_R		0.047
gMVP		0.28
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

Other links and lift over

dbSNP: rs141138840; hg19: chr1-35453877;