NM_173543.3:c.2239A>C

Variant names:

• chr3-138062881-T-G
• rs1191943533
• NM_173543.3:c.2239A>C

Variant summary

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

The NM_173543.3(DZIP1L):​c.2239A>C​(p.Lys747Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DZIP1L NM_173543.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.944

Genes affected

DZIP1L (HGNC:26551): (DAZ interacting zinc finger protein 1 like) Predicted to enable metal ion binding activity. Involved in cilium assembly and regulation of protein localization. Located in ciliary basal body. Colocalizes with centriole. Implicated in polycystic kidney disease 5. [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=0.044331938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DZIP1L	NM_173543.3	c.2239A>C	p.Lys747Gln	missense_variant	Exon 16 of 16	ENST00000327532.7	NP_775814.2
DZIP1L	XM_005247198.4	c.2323A>C	p.Lys775Gln	missense_variant	Exon 16 of 16		XP_005247255.1
DZIP1L	XM_047447642.1	c.2182A>C	p.Lys728Gln	missense_variant	Exon 15 of 15		XP_047303598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DZIP1L	ENST00000327532.7	c.2239A>C	p.Lys747Gln	missense_variant	Exon 16 of 16	1	NM_173543.3	ENSP00000332148.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74354

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.73
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.016
Sift	Benign	0.26	T
Sift4G	Benign	0.36	T
Polyphen		0.020	B
Vest4		0.067
MutPred		0.13		Loss of methylation at K747 (P = 0.0098);
MVP		0.030
MPC		0.11
ClinPred		0.073	T
GERP RS		2.3
Varity_R		0.061
gMVP		0.097

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: rs1191943533; hg19: chr3-137781723;