NM_001076781.3:c.415T>A

Variant names:

• chr6-27400785-T-A
• rs202206704
• NM_001076781.3:c.415T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001076781.3(ZNF391):​c.415T>A​(p.Cys139Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. C139R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF391 NM_001076781.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• Publications: 0 publications found

Genes affected

ZNF391 (HGNC:18779): (zinc finger protein 391) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001076781.3. 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
	ZNF391	NM_001076781.3	MANE Select	c.415T>A	p.Cys139Ser	missense	Exon 3 of 3	NP_001070249.1	Q9UJN7
	ZNF391	NM_001322288.2		c.415T>A	p.Cys139Ser	missense	Exon 4 of 4	NP_001309217.1	Q9UJN7
	ZNF391	NM_001322289.2		c.415T>A	p.Cys139Ser	missense	Exon 4 of 4	NP_001309218.1	Q9UJN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF391	ENST00000244576.9	TSL:2 MANE Select	c.415T>A	p.Cys139Ser	missense	Exon 3 of 3	ENSP00000244576.4	Q9UJN7
	ZNF391	ENST00000901127.1		c.415T>A	p.Cys139Ser	missense	Exon 3 of 3	ENSP00000571186.1
	ZNF391	ENST00000901128.1		c.415T>A	p.Cys139Ser	missense	Exon 2 of 2	ENSP00000571187.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
PhyloP100		4.3
Varity_R		0.87
gMVP		0.19
Mutation Taster		=79/21	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs202206704; hg19: chr6-27368564;