19-57720980-T-C

Variant names:

• chr19-57720980-T-C
• NM_024833.3:c.1106A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024833.3(ZNF671):​c.1106A>G​(p.Tyr369Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF671 NM_024833.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0190

Genes affected

ZNF671 (HGNC:26279): (zinc finger protein 671) 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]

ENSG00000269026 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34047812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF671	NM_024833.3	c.1106A>G	p.Tyr369Cys	missense_variant	Exon 4 of 4	ENST00000317398.10	NP_079109.2
ZNF671	NM_001321376.2	c.875A>G	p.Tyr292Cys	missense_variant	Exon 5 of 5		NP_001308305.1
ZNF671	NM_001321375.2	c.812A>G	p.Tyr271Cys	missense_variant	Exon 3 of 3		NP_001308304.1
ZNF671	XM_017027314.2	c.875A>G	p.Tyr292Cys	missense_variant	Exon 4 of 4		XP_016882803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF671	ENST00000317398.10	c.1106A>G	p.Tyr369Cys	missense_variant	Exon 4 of 4	1	NM_024833.3	ENSP00000321848.5
ENSG00000269026	ENST00000594684.1	c.34-29805T>C		intron_variant	Intron 1 of 2	1		ENSP00000472160.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1106A>G (p.Y369C) alteration is located in exon 4 (coding exon 4) of the ZNF671 gene. This alteration results from a A to G substitution at nucleotide position 1106, causing the tyrosine (Y) at amino acid position 369 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.022
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Benign	0.058
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.64		Gain of disorder (P = 0.0424);
MVP		0.51
MPC		0.73
ClinPred		0.99	D
GERP RS		1.9
Varity_R		0.43
gMVP		0.17

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: chr19-58232348;