rs2058899

Positions:

• chr2-71352999-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014497.5(ZNF638):​c.1318-2720G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,976 control chromosomes in the GnomAD database, including 19,019 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (19019 hom., cov: 31)
• Consequence: ZNF638 NM_014497.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

Genes affected

ZNF638 (HGNC:17894): (zinc finger protein 638) The protein encoded by this gene is a nucleoplasmic protein. It binds cytidine-rich sequences in double-stranded DNA. This protein has three types of domains: MH1, MH2 (repeated three times) and MH3. It is associated with packaging, transferring, or processing transcripts. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF638	NM_014497.5	c.1318-2720G>A		intron_variant		ENST00000264447.9
ZNF638	NM_001014972.3	c.1318-2720G>A		intron_variant
ZNF638	NM_001252612.2	c.1318-2720G>A		intron_variant
ZNF638	NM_001252613.2	c.1318-2720G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF638	ENST00000264447.9	c.1318-2720G>A		intron_variant		1	NM_014497.5	P1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72957 AN: 151858 Hom.: 19026 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.480 AC: 72964 AN: 151976 Hom.: 19019 Cov.: 31 AF XY: 0.482 AC XY: 35774 AN XY: 74262

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.501

Alfa AF: 0.515 Hom.: 4066

Bravo AF: 0.476

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.1
DANN	Benign	0.77

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: rs2058899; hg19: chr2-71580129;