rs61741445

Variant names:

• chr1-34988872-C-G
• rs61741445
• NM_007167.4:c.2210G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-34988872-C-G
• chr1-34988872-C-A

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.2210G>C​(p.Arg737Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,610,374 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (24 hom.)
• Consequence: ZMYM6 NM_007167.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0140
• Publications: 10 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=0.0036462545).
• BP6: Variant 1-34988872-C-G is Benign according to our data. Variant chr1-34988872-C-G is described in ClinVar as Benign. ClinVar VariationId is 3043128.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 263 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.2210G>C	p.Arg737Thr	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.2210G>C	p.Arg737Thr	missense	Exon 16 of 16	ENSP00000349708.4	O95789-3
	ZMYM6	ENST00000493328.5	TSL:1	n.3534G>C		non_coding_transcript_exon	Exon 15 of 15
	ENSG00000271741	ENST00000487874.1	TSL:5	n.2146+3362G>C		intron	N/A	ENSP00000421752.1

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 265 AN: 152122 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00292 AC: 700 AN: 239496 AF XY: 0.00326

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.000767

Gnomad ASJ exome AF: 0.0174

Gnomad EAS exome AF: 0.00193

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000809

Gnomad OTH exome AF: 0.00389

GnomAD4 exome AF: 0.00164 AC: 2394 AN: 1458134 Hom.: 24 Cov.: 31 AF XY: 0.00191 AC XY: 1387 AN XY: 725002

African (AFR) AF: 0.00315 AC: 105 AN: 33380

American (AMR) AF: 0.000766 AC: 34 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 463 AN: 26026

East Asian (EAS) AF: 0.00144 AC: 57 AN: 39594

South Asian (SAS) AF: 0.0101 AC: 862 AN: 85388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53212

Middle Eastern (MID) AF: 0.00955 AC: 55 AN: 5762

European-Non Finnish (NFE) AF: 0.000593 AC: 658 AN: 1110168

Other (OTH) AF: 0.00266 AC: 160 AN: 60240

GnomAD4 genome AF: 0.00173 AC: 263 AN: 152240 Hom.: 1 Cov.: 33 AF XY: 0.00187 AC XY: 139 AN XY: 74438

African (AFR) AF: 0.00246 AC: 102 AN: 41542

American (AMR) AF: 0.000393 AC: 6 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5186

South Asian (SAS) AF: 0.00891 AC: 43 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000662 AC: 45 AN: 68006

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00250 Hom.: 3

Bravo AF: 0.00161

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00196 AC: 7

ESP6500EA AF: 0.00135 AC: 11

ExAC AF: 0.00273 AC: 329

Asia WGS AF: 0.00694 AC: 24 AN: 3474

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	0.13
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.014
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.16
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.040	D
Polyphen		0.32	B
Vest4		0.59
MVP		0.048
MPC		0.50
ClinPred		0.011	T
GERP RS		1.6
Varity_R		0.082
gMVP		0.26
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61741445; hg19: chr1-35454473; COSMIC: COSV99055326; COSMIC: COSV99055326;