chr19-20624738-C-A

Variant names:

• chr19-20624738-C-A
• rs782512962
• NM_001076675.3:c.1139G>T

Variant summary

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

The NM_001076675.3(ZNF626):​c.1139G>T​(p.Arg380Leu) 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. 12/18 in silico tools predict a benign 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. R380Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF626 NM_001076675.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

Genes affected

ZNF626 (HGNC:30461): (zinc finger protein 626) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269110 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06603208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF626	NM_001076675.3	c.1139G>T	p.Arg380Leu	missense_variant	Exon 4 of 4	ENST00000601440.6	NP_001070143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF626	ENST00000601440.6	c.1139G>T	p.Arg380Leu	missense_variant	Exon 4 of 4	4	NM_001076675.3	ENSP00000469958.1
ENSG00000269110	ENST00000595094.1	n.363+20946G>T		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.38
DANN	Benign	0.19
DEOGEN2	Benign	0.0047	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.15	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;.
Sift4G	Benign	0.72	T;T
Polyphen		0.0050	B;.
Vest4		0.14
MutPred		0.30		Loss of MoRF binding (P = 0.033);Loss of MoRF binding (P = 0.033);
MVP		0.072
MPC		0.061
ClinPred		0.021	T
GERP RS		-1.8
Varity_R		0.038
gMVP		0.032

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: rs782512962; hg19: chr19-20807544; COSMIC: COSV74130382; COSMIC: COSV74130382;