7-44756536-C-T

Variant names:

• chr7-44756536-C-T
• NM_031449.4:c.162C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_031449.4(ZMIZ2):​c.162C>T​(p.Ser54Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZMIZ2 NM_031449.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.92
• Publications: 0 publications found

Genes affected

ZMIZ2 (HGNC:22229): (zinc finger MIZ-type containing 2) ZMIZ2 and ZMIZ1 (MIM 607159) are members of a PIAS (see MIM 603566)-like family of proteins that interact with nuclear hormone receptors. ZMIZ2 interacts with androgen receptor (AR; MIM 313700) and enhances AR-mediated transcription (Huang et al., 2005 [PubMed 16051670]).[supplied by OMIM, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 7-44756536-C-T is Benign according to our data. Variant chr7-44756536-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.91 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031449.4. 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
	ZMIZ2	NM_031449.4	MANE Select	c.162C>T	p.Ser54Ser	synonymous	Exon 3 of 19	NP_113637.3
	ZMIZ2	NM_174929.2		c.162C>T	p.Ser54Ser	synonymous	Exon 2 of 17	NP_777589.2	Q8NF64-2
	ZMIZ2	NM_001300959.2		c.162C>T	p.Ser54Ser	synonymous	Exon 3 of 18	NP_001287888.1	Q8NF64-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ2	ENST00000309315.9	TSL:2 MANE Select	c.162C>T	p.Ser54Ser	synonymous	Exon 3 of 19	ENSP00000311778.4	Q8NF64-1
	ZMIZ2	ENST00000441627.5	TSL:1	c.162C>T	p.Ser54Ser	synonymous	Exon 2 of 18	ENSP00000414723.1	Q8NF64-1
	ZMIZ2	ENST00000413916.5	TSL:1	c.162C>T	p.Ser54Ser	synonymous	Exon 3 of 18	ENSP00000409648.1	Q8NF64-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461618 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727106

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		1.9
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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

hg19: chr7-44796135;