rs143254972

Variant names:

• chr13-95584820-G-T
• rs143254972
• NM_198968.4:c.2440C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-95584820-G-T
• chr13-95584820-G-A
• chr13-95584820-G-C

Variant summary

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

The NM_198968.4(DZIP1):​c.2440C>A​(p.Pro814Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: DZIP1 NM_198968.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0140
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06808606).

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.2440C>A	p.Pro814Thr	missense	Exon 22 of 23	NP_945319.1	Q86YF9-1
	DZIP1	NM_014934.5		c.2383C>A	p.Pro795Thr	missense	Exon 21 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.2440C>A	p.Pro814Thr	missense	Exon 22 of 23	ENSP00000366025.2	Q86YF9-1
	DZIP1	ENST00000361396.6	TSL:1	c.2383C>A	p.Pro795Thr	missense	Exon 21 of 22	ENSP00000355175.2	Q86YF9-2
	DZIP1	ENST00000926439.1		c.2494C>A	p.Pro832Thr	missense	Exon 19 of 20	ENSP00000596498.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251388 AF XY: 0.0000147

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000315 AC: 46 AN: 1461818 Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1111968

Other (OTH) AF: 0.0000331 AC: 2 AN: 60392

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74322

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000824 AC: 1

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	0.063
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.63
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.014
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.093
Sift	Benign	0.17	T
Sift4G	Benign	0.56	T
Polyphen		0.0050	B
Vest4		0.18
MutPred		0.31		Loss of catalytic residue at P814 (P = 0.0028)
MVP		0.41
MPC		0.087
ClinPred		0.018	T
GERP RS		3.5
Varity_R		0.036
gMVP		0.046
Mutation Taster		=95/5	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: rs143254972; hg19: chr13-96237074;