13-95589191-T-A

Position:

• chr13-95589191-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198968.4(DZIP1):​c.1990A>T​(p.Met664Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 1,606,368 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.018 (78 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (73 hom.)
• Consequence: DZIP1 NM_198968.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.22

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023871958).
• BP6: Variant 13-95589191-T-A is Benign according to our data. Variant chr13-95589191-T-A is described in ClinVar as [Benign]. Clinvar id is 776804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZIP1	NM_198968.4	c.1990A>T	p.Met664Leu	missense_variant	19/23	ENST00000376829.7	NP_945319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DZIP1	ENST00000376829.7	c.1990A>T	p.Met664Leu	missense_variant	19/23	1	NM_198968.4	ENSP00000366025.2
DZIP1	ENST00000361396.6	c.1933A>T	p.Met645Leu	missense_variant	18/22	1		ENSP00000355175.2
DZIP1	ENST00000347108.7	c.1990A>T	p.Met664Leu	missense_variant	17/21	5		ENSP00000257312.5
DZIP1	ENST00000361156.7	c.1933A>T	p.Met645Leu	missense_variant	16/20	5		ENSP00000355018.3

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2740 AN: 152192 Hom.: 77 Cov.: 33

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00470 AC: 1156 AN: 245950 Hom.: 20 AF XY: 0.00325 AC XY: 432 AN XY: 132808

Gnomad AFR exome AF: 0.0605

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.000402

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000244

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000453

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00227 AC: 3302 AN: 1454058 Hom.: 73 Cov.: 29 AF XY: 0.00203 AC XY: 1471 AN XY: 723054

Gnomad4 AFR exome AF: 0.0653

Gnomad4 AMR exome AF: 0.00402

Gnomad4 ASJ exome AF: 0.000538

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000262

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000543

Gnomad4 OTH exome AF: 0.00524

GnomAD4 genome AF: 0.0181 AC: 2754 AN: 152310 Hom.: 78 Cov.: 33 AF XY: 0.0174 AC XY: 1297 AN XY: 74488

Gnomad4 AFR AF: 0.0618

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.0207

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0586 AC: 258

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00574 AC: 697

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.000878

EpiControl AF: 0.000892

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 08, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.069
DANN	Benign	0.44
DEOGEN2	Benign	0.017	.;T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.55	.;T;T;.
MetaRNN	Benign	0.0024	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;N;.;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.090	N;N;N;N
REVEL	Benign	0.0090
Sift	Benign	0.46	T;T;T;T
Sift4G	Benign	0.80	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.091
MutPred		0.26		.;Gain of catalytic residue at M664 (P = 0.002);.;Gain of catalytic residue at M664 (P = 0.002);
MVP		0.24
MPC		0.071
ClinPred		0.0016	T
GERP RS		-6.8
Varity_R		0.045
gMVP		0.070

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

Publications

LitVar

Other links and lift over

dbSNP: rs34303958; hg19: chr13-96241445;