2-71349354-C-G

Variant names:

• chr2-71349354-C-G
• rs772720043
• NM_014497.5:c.400C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014497.5(ZNF638):​c.400C>G​(p.Arg134Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R134C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF638 NM_014497.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2870061).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014497.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF638	NM_014497.5	MANE Select	c.400C>G	p.Arg134Gly	missense	Exon 2 of 28	NP_055312.2
	ZNF638	NM_001014972.3		c.400C>G	p.Arg134Gly	missense	Exon 2 of 28	NP_001014972.1	Q14966-1
	ZNF638	NM_001252612.2		c.400C>G	p.Arg134Gly	missense	Exon 2 of 28	NP_001239541.1	Q14966-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF638	ENST00000264447.9	TSL:1 MANE Select	c.400C>G	p.Arg134Gly	missense	Exon 2 of 28	ENSP00000264447.4	Q14966-1
	ZNF638	ENST00000409544.5	TSL:1	c.400C>G	p.Arg134Gly	missense	Exon 2 of 28	ENSP00000386433.1	Q14966-1
	ZNF638	ENST00000410075.6	TSL:1	c.718C>G	p.Arg240Gly	missense	Exon 2 of 13	ENSP00000485608.2	A0ABJ7FB56

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.065	D
MutationAssessor	Benign	1.0	L
PhyloP100		3.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.18		Loss of MoRF binding (P = 0.02)
MVP		0.25
MPC		0.27
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.38
gMVP		0.19
Mutation Taster		=73/27	polymorphism

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: rs772720043; hg19: chr2-71576484;