rs780339766

Variant names:

• chr19-53140823-C-A
• rs780339766
• NM_032584.3:c.2005G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-53140823-C-A
• chr19-53140823-C-T

Variant summary

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

The NM_032584.3(ZNF347):​c.2005G>T​(p.Ala669Ser) 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. 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. A669T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF347 NM_032584.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

Genes affected

ZNF347 (HGNC:16447): (zinc finger protein 347) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.045348674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF347	NM_032584.3	c.2005G>T	p.Ala669Ser	missense_variant	Exon 5 of 5	ENST00000334197.12	NP_115973.2
ZNF347	NM_001172674.2	c.2008G>T	p.Ala670Ser	missense_variant	Exon 5 of 5		NP_001166145.1
ZNF347	NM_001172675.2	c.2008G>T	p.Ala670Ser	missense_variant	Exon 5 of 5		NP_001166146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF347	ENST00000334197.12	c.2005G>T	p.Ala669Ser	missense_variant	Exon 5 of 5	1	NM_032584.3	ENSP00000334146.6
ZNF347	ENST00000452676.6	c.2008G>T	p.Ala670Ser	missense_variant	Exon 5 of 5	2		ENSP00000405218.2
ZNF347	ENST00000601469.2	c.2008G>T	p.Ala670Ser	missense_variant	Exon 5 of 5	2		ENSP00000471712.2
ZNF347	ENST00000601804.5	c.97+7858G>T		intron_variant	Intron 3 of 3	4		ENSP00000470590.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.39
DEOGEN2	Benign	0.021	T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.36	T;T;.
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.0	N;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.95	N;N;.
REVEL	Benign	0.0090
Sift	Benign	0.16	T;T;.
Sift4G	Benign	0.60	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.020
MutPred		0.32		Gain of disorder (P = 0.0252);.;.;
MVP		0.15
MPC		0.013
ClinPred		0.16	T
GERP RS		-5.9
Varity_R		0.044
gMVP		0.031

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: rs780339766; hg19: chr19-53644076;