rs376504755

Variant names:

• chr19-56441634-C-A
• rs376504755
• NM_001321356.2:c.1361G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-56441634-C-A
• chr19-56441634-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321356.2(ZNF667):​c.1361G>T​(p.Arg454Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R454H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ZNF667 NM_001321356.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

Genes affected

ZNF667 (HGNC:28854): (zinc finger protein 667) 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20042592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF667	NM_001321356.2	c.1361G>T	p.Arg454Leu	missense_variant	Exon 7 of 7	ENST00000504904.8	NP_001308285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF667	ENST00000504904.8	c.1361G>T	p.Arg454Leu	missense_variant	Exon 7 of 7	2	NM_001321356.2	ENSP00000439402.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;T;T
Eigen	Benign	-0.057
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.47	.;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-3.5	D;D;.
REVEL	Benign	0.14
Sift	Benign	0.13	T;T;.
Sift4G	Benign	0.28	T;T;T
Polyphen		0.98	D;D;.
Vest4		0.35
MVP		0.40
MPC		0.59
ClinPred		0.86	D
GERP RS		3.9
Varity_R		0.25
gMVP		0.35

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: rs376504755; hg19: chr19-56953003;