13-19851747-C-G

Variant names:

• chr13-19851747-C-G
• rs760543043
• NM_001142684.2:c.434G>C

Variant summary

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

The NM_001142684.2(ZMYM5):​c.434G>C​(p.Gly145Ala) 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. G145E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZMYM5 NM_001142684.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 0 publications found

Genes affected

ZMYM5 (HGNC:13029): (zinc finger MYM-type containing 5) Predicted to enable zinc ion binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZMYM5 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: 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=0.078742534).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142684.2. 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
	ZMYM5	NM_001142684.2	MANE Select	c.434G>C	p.Gly145Ala	missense	Exon 3 of 8	NP_001136156.1	Q9UJ78-4
	ZMYM5	NM_001039650.3		c.434G>C	p.Gly145Ala	missense	Exon 3 of 6	NP_001034739.1	Q9UJ78-1
	ZMYM5	NM_001039649.3		c.434G>C	p.Gly145Ala	missense	Exon 3 of 5	NP_001034738.1	Q9UJ78-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM5	ENST00000337963.9	TSL:5 MANE Select	c.434G>C	p.Gly145Ala	missense	Exon 3 of 8	ENSP00000337034.4	Q9UJ78-4
	ZMYM5	ENST00000382905.8	TSL:1	c.434G>C	p.Gly145Ala	missense	Exon 3 of 6	ENSP00000372361.4	Q9UJ78-1
	ZMYM5	ENST00000382907.8	TSL:1	c.434G>C	p.Gly145Ala	missense	Exon 3 of 5	ENSP00000372364.4	Q9UJ78-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.5
DANN	Benign	0.81
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L
PhyloP100		0.11
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.034
Sift	Uncertain	0.024	D
Sift4G	Benign	0.24	T
Polyphen		0.057	B
Vest4		0.055
MutPred		0.16		Loss of disorder (P = 0.1365)
MVP		0.014
MPC		0.019
ClinPred		0.072	T
GERP RS		-1.5
Varity_R		0.038
gMVP		0.095
Mutation Taster		=84/16	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: rs760543043; hg19: chr13-20425887;