NM_197968.4:c.140A>C

Variant names:

• chr13-19993212-A-C
• rs557142117
• NM_197968.4:c.140A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_197968.4(ZMYM2):​c.140A>C​(p.Asn47Thr) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N47S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZMYM2 NM_197968.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 2 publications found

Genes affected

ZMYM2 (HGNC:12989): (zinc finger MYM-type containing 2) The protein encoded by this gene is a zinc finger protein that may act as a transcription factor. The encoded protein may be part of a BHC histone deacetylase complex. Translocation of this gene with the fibroblast growth factor receptor-1 gene (FGFR1) results in a fusion gene, which may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]

ZMYM2 Gene-Disease associations (from GenCC):

• neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Franklin by Genoox, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09208846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197968.4. 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
	ZMYM2	NM_197968.4	MANE Select	c.140A>C	p.Asn47Thr	missense	Exon 3 of 25	NP_932072.1	Q9UBW7-1
	ZMYM2	NM_001190964.4		c.140A>C	p.Asn47Thr	missense	Exon 4 of 26	NP_001177893.1	Q9UBW7-1
	ZMYM2	NM_001190965.4		c.140A>C	p.Asn47Thr	missense	Exon 3 of 25	NP_001177894.1	Q9UBW7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM2	ENST00000610343.5	TSL:1 MANE Select	c.140A>C	p.Asn47Thr	missense	Exon 3 of 25	ENSP00000479904.1	Q9UBW7-1
	ZMYM2	ENST00000382871.3	TSL:1	c.140A>C	p.Asn47Thr	missense	Exon 4 of 26	ENSP00000372324.2	Q9UBW7-1
	ZMYM2	ENST00000382874.6	TSL:1	c.140A>C	p.Asn47Thr	missense	Exon 4 of 26	ENSP00000372327.2	Q9UBW7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.63
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.11
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.046
Sift	Benign	0.046	D
Sift4G	Benign	0.090	T
Polyphen		0.0050	B
Vest4		0.21
MutPred		0.28		Gain of catalytic residue at L42 (P = 0.0057)
MVP		0.25
ClinPred		0.12	T
GERP RS		-4.6
Varity_R		0.099
gMVP		0.081
Mutation Taster		=83/17	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: rs557142117; hg19: chr13-20567352;