chr13-95586062-C-G

Variant names:

• chr13-95586062-C-G
• rs767605428
• NM_198968.4:c.2293G>C

Variant summary

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

The NM_198968.4(DZIP1):​c.2293G>C​(p.Gly765Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,920 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G765S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: DZIP1 NM_198968.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.836
• Publications: 2 publications found

Genes affected

DZIP1 (HGNC:20908): (DAZ interacting zinc finger protein 1) Predicted to enable metal ion binding activity. Involved in cilium assembly; germ cell development; and spermatogenesis. Located in cytosol; microtubule organizing center; and nucleoplasm. Colocalizes with centriole. Implicated in mitral valve prolapse and spermatogenic failure 47. [provided by Alliance of Genome Resources, Apr 2022]

DZIP1 Gene-Disease associations (from GenCC):

• spermatogenic failure 47

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198968.4. 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
	DZIP1	NM_198968.4	MANE Select	c.2293G>C	p.Gly765Arg	missense	Exon 21 of 23	NP_945319.1	Q86YF9-1
	DZIP1	NM_014934.5		c.2236G>C	p.Gly746Arg	missense	Exon 20 of 22	NP_055749.1	Q86YF9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZIP1	ENST00000376829.7	TSL:1 MANE Select	c.2293G>C	p.Gly765Arg	missense	Exon 21 of 23	ENSP00000366025.2	Q86YF9-1
	DZIP1	ENST00000361396.6	TSL:1	c.2236G>C	p.Gly746Arg	missense	Exon 20 of 22	ENSP00000355175.2	Q86YF9-2
	DZIP1	ENST00000926439.1		c.2347G>C	p.Gly783Arg	missense	Exon 18 of 20	ENSP00000596498.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247444 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1457920 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 725064

African (AFR) AF: 0.00 AC: 0 AN: 33236

American (AMR) AF: 0.00 AC: 0 AN: 44000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39372

South Asian (SAS) AF: 0.00 AC: 0 AN: 85282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110644

Other (OTH) AF: 0.00 AC: 0 AN: 60224

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000549

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.036
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.84
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.72
MutPred		0.41		Gain of loop (P = 3e-04)
MVP		0.58
MPC		0.10
ClinPred		0.86	D
GERP RS		2.8
Varity_R		0.20
gMVP		0.26
Mutation Taster		=88/12	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: rs767605428; hg19: chr13-96238316;