NM_014497.5:c.1318-2720G>A

Variant names:

• chr2-71352999-G-A
• rs2058899
• NM_014497.5:c.1318-2720G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF638	NM_014497.5	c.1318-2720G>A		intron_variant	Intron 2 of 27	ENST00000264447.9	NP_055312.2
ZNF638	NM_001014972.3	c.1318-2720G>A		intron_variant	Intron 2 of 27		NP_001014972.1
ZNF638	NM_001252612.2	c.1318-2720G>A		intron_variant	Intron 2 of 27		NP_001239541.1
ZNF638	NM_001252613.2	c.1318-2720G>A		intron_variant	Intron 2 of 27		NP_001239542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF638	ENST00000264447.9	c.1318-2720G>A		intron_variant	Intron 2 of 27	1	NM_014497.5	ENSP00000264447.4

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

African (AFR) AF: 0.269 AC: 11133 AN: 41454

American (AMR) AF: 0.608 AC: 9295 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2097 AN: 3468

East Asian (EAS) AF: 0.297 AC: 1530 AN: 5158

South Asian (SAS) AF: 0.552 AC: 2661 AN: 4822

European-Finnish (FIN) AF: 0.533 AC: 5611 AN: 10536

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38908 AN: 67946

Other (OTH) AF: 0.501 AC: 1056 AN: 2108

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
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2058899; hg19: chr2-71580129;