2-71349552-G-A

Position:

• chr2-71349552-G-A

Variant summary

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

The NM_014497.5(ZNF638):​c.598G>A​(p.Gly200Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF638 NM_014497.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

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 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=0.06646183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF638	NM_014497.5	c.598G>A	p.Gly200Ser	missense_variant	2/28	ENST00000264447.9	NP_055312.2
ZNF638	NM_001014972.3	c.598G>A	p.Gly200Ser	missense_variant	2/28		NP_001014972.1
ZNF638	NM_001252612.2	c.598G>A	p.Gly200Ser	missense_variant	2/28		NP_001239541.1
ZNF638	NM_001252613.2	c.598G>A	p.Gly200Ser	missense_variant	2/28		NP_001239542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF638	ENST00000264447.9	c.598G>A	p.Gly200Ser	missense_variant	2/28	1	NM_014497.5	ENSP00000264447	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.598G>A (p.G200S) alteration is located in exon 2 (coding exon 1) of the ZNF638 gene. This alteration results from a G to A substitution at nucleotide position 598, causing the glycine (G) at amino acid position 200 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.027	.;T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.79	T;.;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.066	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N;N;N
MutationTaster	Benign	0.92	N;N;N;N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.71	.;N;N
REVEL	Benign	0.057
Sift	Benign	0.30	.;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.062	.;B;B
Vest4		0.13
MutPred		0.084		Gain of phosphorylation at G200 (P = 0.0261);Gain of phosphorylation at G200 (P = 0.0261);Gain of phosphorylation at G200 (P = 0.0261);
MVP		0.043
MPC		0.041
ClinPred		0.25	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-71576682;