rs2044262951

Variant names:

• chr13-95589834-C-G
• rs2044262951
• NM_198968.4:c.1942G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-95589834-C-G
• chr13-95589834-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198968.4(DZIP1):​c.1942G>C​(p.Ala648Pro) 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. 15/21 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. A648T) 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: -0.0260

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.018724084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DZIP1	NM_198968.4	c.1942G>C	p.Ala648Pro	missense_variant	Exon 18 of 23	ENST00000376829.7	NP_945319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DZIP1	ENST00000376829.7	c.1942G>C	p.Ala648Pro	missense_variant	Exon 18 of 23	1	NM_198968.4	ENSP00000366025.2
DZIP1	ENST00000361396.6	c.1885G>C	p.Ala629Pro	missense_variant	Exon 17 of 22	1		ENSP00000355175.2
DZIP1	ENST00000347108.7	c.1942G>C	p.Ala648Pro	missense_variant	Exon 16 of 21	5		ENSP00000257312.5
DZIP1	ENST00000361156.7	c.1885G>C	p.Ala629Pro	missense_variant	Exon 15 of 20	5		ENSP00000355018.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	10
DANN	Benign	0.62
DEOGEN2	Benign	0.021	.;T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.69	.;T;T;.
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.019	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.83	.;N;.;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.35	N;N;N;N
REVEL	Benign	0.025
Sift	Benign	0.58	T;T;T;T
Sift4G	Benign	0.92	T;T;T;T
Polyphen		0.0010	B;B;B;B
Vest4		0.072
MutPred		0.18		.;Gain of relative solvent accessibility (P = 0.0275);.;Gain of relative solvent accessibility (P = 0.0275);
MVP		0.22
MPC		0.098
ClinPred		0.040	T
GERP RS		-0.61
Varity_R		0.024
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs2044262951; hg19: chr13-96242088; COSMIC: COSV104416745; COSMIC: COSV104416745;