13-95587611-T-C

Variant names:

• chr13-95587611-T-C
• rs374870127
• NM_198968.4:c.2146A>G

Variant summary

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

The NM_198968.4(DZIP1):​c.2146A>G​(p.Thr716Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. T716P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DZIP1 NM_198968.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49

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

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=0.033926576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DZIP1	NM_198968.4	c.2146A>G	p.Thr716Ala	missense_variant	Exon 20 of 23	ENST00000376829.7	NP_945319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DZIP1	ENST00000376829.7	c.2146A>G	p.Thr716Ala	missense_variant	Exon 20 of 23	1	NM_198968.4	ENSP00000366025.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0020
DANN	Benign	0.20
DEOGEN2	Benign	0.024	.;T;.;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.35	.;T;T;.
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.034	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.23	.;N;.;N
PhyloP100		-3.5
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.16	N;N;N;N
REVEL	Benign	0.015
Sift	Benign	0.60	T;T;T;T
Sift4G	Benign	0.68	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.037
MutPred		0.22		.;Loss of phosphorylation at T716 (P = 0.0062);.;Loss of phosphorylation at T716 (P = 0.0062);
MVP		0.27
MPC		0.074
ClinPred		0.015	T
GERP RS		-6.2
Varity_R		0.014
gMVP		0.062
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

dbSNP: rs374870127; hg19: chr13-96239865;