19-56664151-T-A

Variant names:

• chr19-56664151-T-A
• NM_001005850.3:c.1048A>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001005850.3(ZNF835):​c.1048A>T​(p.Thr350Ser) variant causes a missense 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: ZNF835 NM_001005850.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.74

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033333242).
• BP6: Variant 19-56664151-T-A is Benign according to our data. Variant chr19-56664151-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3823172.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF835	NM_001005850.3	c.1048A>T	p.Thr350Ser	missense_variant	Exon 2 of 2	ENST00000537055.4	NP_001005850.2
ZNF835	XM_005259382.3	c.1048A>T	p.Thr350Ser	missense_variant	Exon 2 of 2		XP_005259439.1
ZNF835	XM_005259383.4	c.1048A>T	p.Thr350Ser	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.1048A>T	p.Thr350Ser	missense_variant	Exon 2 of 2	2	NM_001005850.3	ENSP00000444747.1
ZIM2-AS1	ENST00000650950.1	n.202-3126T>A		intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 79

GnomAD4 genome Cov.: 35

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 14, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.82
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.070	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.049
Sift	Benign	0.19	T
Sift4G	Benign	0.25	T
Vest4		0.017
MVP		0.099
ClinPred		0.040	T
GERP RS		-3.1
Varity_R		0.042
gMVP		0.023

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-57175519;