2-71349882-T-A

Position:

• chr2-71349882-T-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.928T>A​(p.Ser310Thr) 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: 0.574

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=0.07393026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF638	NM_014497.5	c.928T>A	p.Ser310Thr	missense_variant	2/28	ENST00000264447.9	NP_055312.2
ZNF638	NM_001014972.3	c.928T>A	p.Ser310Thr	missense_variant	2/28		NP_001014972.1
ZNF638	NM_001252612.2	c.928T>A	p.Ser310Thr	missense_variant	2/28		NP_001239541.1
ZNF638	NM_001252613.2	c.928T>A	p.Ser310Thr	missense_variant	2/28		NP_001239542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF638	ENST00000264447.9	c.928T>A	p.Ser310Thr	missense_variant	2/28	1	NM_014497.5	ENSP00000264447.4

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 12, 2023

The c.928T>A (p.S310T) alteration is located in exon 2 (coding exon 1) of the ZNF638 gene. This alteration results from a T to A substitution at nucleotide position 928, causing the serine (S) at amino acid position 310 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.95
DEOGEN2	Benign	0.044	.;T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.81	T;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.074	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.0	M;M;M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.83	.;N;N
REVEL	Benign	0.065
Sift	Uncertain	0.021	.;D;D
Sift4G	Benign	0.081	T;D;D
Polyphen		0.36	.;B;B
Vest4		0.074
MutPred		0.13		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP		0.11
MPC		0.031
ClinPred		0.21	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.089
gMVP		0.27

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: chr2-71577012;