19-53576888-A-C

Variant names:

• chr19-53576888-A-C
• NM_001079906.2:c.328A>C
• ZNF331 p.Arg110Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001079906.2(ZNF331):​c.328A>C​(p.Arg110Arg) variant causes a synonymous 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF331 NM_001079906.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 0 publications found

Genes affected

ZNF331 (HGNC:15489): (zinc finger protein 331) This gene encodes a zinc finger protein containing a KRAB (Kruppel-associated box) domain found in transcriptional repressors. This gene may be methylated and silenced in cancer cells. This gene is located within a differentially methylated region (DMR) and shows allele-specific expression in placenta. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding the same protein. [provided by RefSeq, Nov 2015]

ENSG00000290755 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=0.487 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079906.2. 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
	ZNF331	NM_001079906.2	MANE Select	c.328A>C	p.Arg110Arg	synonymous	Exon 6 of 6	NP_001073375.1	Q9NQX6
	ZNF331	NM_001079907.1		c.328A>C	p.Arg110Arg	synonymous	Exon 6 of 6	NP_001073376.1	Q9NQX6
	ZNF331	NM_001253798.2		c.328A>C	p.Arg110Arg	synonymous	Exon 7 of 7	NP_001240727.1	Q9NQX6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF331	ENST00000449416.6	TSL:5 MANE Select	c.328A>C	p.Arg110Arg	synonymous	Exon 6 of 6	ENSP00000393817.1	Q9NQX6
	ZNF331	ENST00000253144.13	TSL:1	c.328A>C	p.Arg110Arg	synonymous	Exon 7 of 7	ENSP00000253144.9	Q9NQX6
	ZNF331	ENST00000504493.6	TSL:1	c.328A>C	p.Arg110Arg	synonymous	Exon 5 of 5	ENSP00000425517.2	Q9NQX6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		0.49

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

hg19: chr19-54080142;

COSMIC: COSV99468301;

COSMIC: COSV99468301;