NM_024733.5:c.1896G>C

Variant names:

• chr19-53164594-C-G
• rs755232699
• NM_024733.5:c.1896G>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_024733.5(ZNF665):​c.1896G>C​(p.Gly632Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 151,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF665 NM_024733.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.703
• Publications: 0 publications found

Genes affected

ZNF665 (HGNC:25885): (zinc finger protein 665) 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

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-53164594-C-G is Benign according to our data. Variant chr19-53164594-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3026342.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.703 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024733.5. 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
	ZNF665	NM_024733.5	MANE Select	c.1896G>C	p.Gly632Gly	synonymous	Exon 4 of 4	NP_079009.3
	ZNF665	NM_001353458.2		c.1980G>C	p.Gly660Gly	synonymous	Exon 5 of 5	NP_001340387.1
	ZNF665	NM_001353459.2		c.1896G>C	p.Gly632Gly	synonymous	Exon 4 of 4	NP_001340388.1	Q9H7R5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF665	ENST00000396424.5	TSL:2 MANE Select	c.1896G>C	p.Gly632Gly	synonymous	Exon 4 of 4	ENSP00000379702.2	Q9H7R5
	ZNF665	ENST00000650736.1		c.1896G>C	p.Gly632Gly	synonymous	Exon 5 of 5	ENSP00000498600.1	Q9H7R5
	ZNF665	ENST00000868912.1		c.1896G>C	p.Gly632Gly	synonymous	Exon 4 of 4	ENSP00000538971.1

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 151986 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250966 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000308 AC: 45 AN: 1461182 Hom.: 0 Cov.: 59 AF XY: 0.0000344 AC XY: 25 AN XY: 726904

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1111332

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 151986 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74248

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000242 AC: 1 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.52
PhyloP100		-0.70

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: rs755232699; hg19: chr19-53667847;