chr2-71349300-G-A

Position:

• chr2-71349300-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014497.5(ZNF638):​c.346G>A​(p.Val116Met) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF638 NM_014497.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.867

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09848988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF638	NM_014497.5	c.346G>A	p.Val116Met	missense_variant	2/28	ENST00000264447.9
ZNF638	NM_001014972.3	c.346G>A	p.Val116Met	missense_variant	2/28
ZNF638	NM_001252612.2	c.346G>A	p.Val116Met	missense_variant	2/28
ZNF638	NM_001252613.2	c.346G>A	p.Val116Met	missense_variant	2/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF638	ENST00000264447.9	c.346G>A	p.Val116Met	missense_variant	2/28	1	NM_014497.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.94
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.037
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.87	D;D;.;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.098	T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.34	N;.;N;N
MutationTaster	Benign	0.77	N;N;N;N;N;N
PrimateAI	Benign	0.45	T
REVEL	Benign	0.029
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.062	.;.;B;B
Vest4		0.076
MutPred		0.25		Loss of methylation at K117 (P = 0.0172);Loss of methylation at K117 (P = 0.0172);Loss of methylation at K117 (P = 0.0172);Loss of methylation at K117 (P = 0.0172);
MVP		0.093
MPC		0.041
ClinPred		0.096	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.035
gMVP		0.072

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: rs1573029365; hg19: chr2-71576430;