19-56664212-T-C

Variant names:

• chr19-56664212-T-C
• rs373121194
• NM_001005850.3:c.987A>G

Variant summary

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

The NM_001005850.3(ZNF835):​c.987A>G​(p.Thr329Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000076 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF835 NM_001005850.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -20.0
• Publications: 2 publications found

Genes affected

ZNF835 (HGNC:34332): (zinc finger protein 835) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZIM2-AS1 (HGNC:51304): (ZIM2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-56664212-T-C is Benign according to our data. Variant chr19-56664212-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3341632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-20 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005850.3. 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
	ZNF835	NM_001005850.3	MANE Select	c.987A>G	p.Thr329Thr	synonymous	Exon 2 of 2	NP_001005850.2	Q9Y2P0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF835	ENST00000537055.4	TSL:2 MANE Select	c.987A>G	p.Thr329Thr	synonymous	Exon 2 of 2	ENSP00000444747.1	Q9Y2P0
	ZNF835	ENST00000890488.1		c.987A>G	p.Thr329Thr	synonymous	Exon 2 of 2	ENSP00000560547.1
	ZNF835	ENST00000890489.1		c.987A>G	p.Thr329Thr	synonymous	Exon 2 of 2	ENSP00000560548.1

Frequencies

GnomAD3 genomes AF: 0.00000764 AC: 1 AN: 130902 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000292

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000827 AC: 2 AN: 241900 AF XY: 0.00000760

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: 0.0000488

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000169

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000139 AC: 20 AN: 1439102 Hom.: 0 Cov.: 83 AF XY: 0.0000154 AC XY: 11 AN XY: 715938

⚠️ 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: 32912

American (AMR) AF: 0.00 AC: 0 AN: 42794

Ashkenazi Jewish (ASJ) AF: 0.0000392 AC: 1 AN: 25500

East Asian (EAS) AF: 0.00 AC: 0 AN: 39028

South Asian (SAS) AF: 0.00 AC: 0 AN: 84716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.0000155 AC: 17 AN: 1097736

Other (OTH) AF: 0.0000338 AC: 2 AN: 59258

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000763 AC: 1 AN: 131042 Hom.: 0 Cov.: 34 AF XY: 0.0000156 AC XY: 1 AN XY: 64262

African (AFR) AF: 0.0000291 AC: 1 AN: 34388

American (AMR) AF: 0.00 AC: 0 AN: 13450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3156

East Asian (EAS) AF: 0.00 AC: 0 AN: 4072

South Asian (SAS) AF: 0.00 AC: 0 AN: 4106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 186

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60400

Other (OTH) AF: 0.00 AC: 0 AN: 1798

Alfa AF: 0.000786 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	-0.94
CADD	Benign	7.6
DANN	Benign	0.32
PhyloP100		-20
Mutation Taster		=100/0	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: rs373121194; hg19: chr19-57175580;