19-56664276-C-T

Variant names:

• chr19-56664276-C-T
• rs762463668
• NM_001005850.3:c.923G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001005850.3(ZNF835):​c.923G>A​(p.Cys308Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000963 in 1,454,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. C308F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: ZNF835 NM_001005850.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF835	NM_001005850.3	c.923G>A	p.Cys308Tyr	missense_variant	Exon 2 of 2	ENST00000537055.4	NP_001005850.2
ZNF835	XM_005259382.3	c.923G>A	p.Cys308Tyr	missense_variant	Exon 2 of 2		XP_005259439.1
ZNF835	XM_005259383.4	c.923G>A	p.Cys308Tyr	missense_variant	Exon 2 of 2		XP_005259440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF835	ENST00000537055.4	c.923G>A	p.Cys308Tyr	missense_variant	Exon 2 of 2	2	NM_001005850.3	ENSP00000444747.1
ZIM2-AS1	ENST00000650950.1	n.202-3001C>T		intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD3 exomes AF: 0.00000859 AC: 2 AN: 232876 Hom.: 0 AF XY: 0.0000158 AC XY: 2 AN XY: 126834

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000193

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000963 AC: 14 AN: 1454086 Hom.: 0 Cov.: 81 AF XY: 0.0000166 AC XY: 12 AN XY: 722996

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

Bravo AF: 0.00000378

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.40
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Pathogenic	3.8	H
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.51
MVP		0.38
ClinPred		1.0	D
GERP RS		2.1
Varity_R		0.84
gMVP		0.19

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: rs762463668; hg19: chr19-57175644;