13-19851738-T-C

Variant names:

• chr13-19851738-T-C
• rs767455995
• NM_001142684.2:c.443A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142684.2(ZMYM5):​c.443A>G​(p.Asn148Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,433,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: ZMYM5 NM_001142684.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05127743).

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.443A>G	p.Asn148Ser	missense	Exon 3 of 8	NP_001136156.1	Q9UJ78-4
	ZMYM5	NM_001039650.3		c.443A>G	p.Asn148Ser	missense	Exon 3 of 6	NP_001034739.1	Q9UJ78-1
	ZMYM5	NM_001039649.3		c.443A>G	p.Asn148Ser	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.443A>G	p.Asn148Ser	missense	Exon 3 of 8	ENSP00000337034.4	Q9UJ78-4
	ZMYM5	ENST00000382905.8	TSL:1	c.443A>G	p.Asn148Ser	missense	Exon 3 of 6	ENSP00000372361.4	Q9UJ78-1
	ZMYM5	ENST00000382907.8	TSL:1	c.443A>G	p.Asn148Ser	missense	Exon 3 of 5	ENSP00000372364.4	Q9UJ78-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000316 AC: 7 AN: 221866 AF XY: 0.0000250

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000420

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000558 AC: 8 AN: 1433368 Hom.: 0 Cov.: 31 AF XY: 0.00000421 AC XY: 3 AN XY: 712558

African (AFR) AF: 0.00 AC: 0 AN: 31528

American (AMR) AF: 0.00 AC: 0 AN: 35716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24238

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 80366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52748

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104480

Other (OTH) AF: 0.0000169 AC: 1 AN: 59102

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.6
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.051
Sift	Benign	0.13	T
Sift4G	Benign	0.42	T
Polyphen		0.010	B
Vest4		0.10
MutPred		0.16		Gain of glycosylation at N148 (P = 0.0376)
MVP		0.040
MPC		0.095
ClinPred		0.054	T
GERP RS		0.075
Varity_R		0.022
gMVP		0.056
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs767455995; hg19: chr13-20425878;