1-34988170-T-G

Variant names:

• chr1-34988170-T-G
• rs61743186
• NM_007167.4:c.2912A>C

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.2912A>C​(p.Asn971Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,549,882 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (19 hom.)
• Consequence: ZMYM6 NM_007167.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.27
• Publications: 7 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=0.008333147).
• BP6: Variant 1-34988170-T-G is Benign according to our data. Variant chr1-34988170-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3043412.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 512 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.2912A>C	p.Asn971Thr	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.2912A>C	p.Asn971Thr	missense	Exon 16 of 16	ENSP00000349708.4	O95789-3
	ZMYM6	ENST00000493328.5	TSL:1	n.4236A>C		non_coding_transcript_exon	Exon 15 of 15
	ENSG00000271741	ENST00000487874.1	TSL:5	n.2146+4064A>C		intron	N/A	ENSP00000421752.1

Frequencies

GnomAD3 genomes AF: 0.00336 AC: 512 AN: 152228 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00541

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00303 AC: 457 AN: 150846 AF XY: 0.00300

Gnomad AFR exome AF: 0.000637

Gnomad AMR exome AF: 0.00339

Gnomad ASJ exome AF: 0.00366

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000590

Gnomad NFE exome AF: 0.00535

Gnomad OTH exome AF: 0.00419

GnomAD4 exome AF: 0.00465 AC: 6500 AN: 1397536 Hom.: 19 Cov.: 32 AF XY: 0.00460 AC XY: 3170 AN XY: 689006

African (AFR) AF: 0.000730 AC: 23 AN: 31526

American (AMR) AF: 0.00357 AC: 127 AN: 35542

Ashkenazi Jewish (ASJ) AF: 0.00278 AC: 70 AN: 25148

East Asian (EAS) AF: 0.00 AC: 0 AN: 35706

South Asian (SAS) AF: 0.000343 AC: 27 AN: 78718

European-Finnish (FIN) AF: 0.000652 AC: 32 AN: 49098

Middle Eastern (MID) AF: 0.00316 AC: 18 AN: 5694

European-Non Finnish (NFE) AF: 0.00554 AC: 5968 AN: 1078170

Other (OTH) AF: 0.00406 AC: 235 AN: 57934

GnomAD4 genome AF: 0.00336 AC: 512 AN: 152346 Hom.: 2 Cov.: 33 AF XY: 0.00303 AC XY: 226 AN XY: 74500

African (AFR) AF: 0.00106 AC: 44 AN: 41584

American (AMR) AF: 0.00451 AC: 69 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

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

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

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00541 AC: 368 AN: 68026

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00465 Hom.: 0

Bravo AF: 0.00367

TwinsUK AF: 0.00485 AC: 18

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00570 AC: 28

ExAC AF: 0.00237 AC: 51

ClinVar

ClinVar submissions

Significance: Likely 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	0.15
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.069
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.0083	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.0090
Sift	Uncertain	0.016	D
Sift4G	Benign	0.30	T
Polyphen		0.19	B
Vest4		0.34
MVP		0.067
MPC		0.54
ClinPred		0.018	T
GERP RS		3.2
Varity_R		0.093
gMVP		0.16
Mutation Taster		=96/4	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: rs61743186; hg19: chr1-35453771; COSMIC: COSV64120513; COSMIC: COSV64120513;