1-90937587-G-C

Position:

• chr1-90937587-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_201269.3(ZNF644):​c.3586C>G​(p.Gln1196Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ZNF644 NM_201269.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.89

Genes affected

ZNF644 (HGNC:29222): (zinc finger protein 644) The protein encoded by this gene is a zinc finger transcription factor that may play a role in eye development. Defects in this gene have been associated with high myopia. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF644	NM_201269.3	c.3586C>G	p.Gln1196Glu	missense_variant	4/6	ENST00000337393.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF644	ENST00000337393.10	c.3586C>G	p.Gln1196Glu	missense_variant	4/6	1	NM_201269.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461666 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727134

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2022

The c.3586C>G (p.Q1196E) alteration is located in exon 4 (coding exon 3) of the ZNF644 gene. This alteration results from a C to G substitution at nucleotide position 3586, causing the glutamine (Q) at amino acid position 1196 to be replaced by a glutamic acid (E). 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	Benign	0.24
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T
Eigen	Uncertain	0.60
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.69	N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.072	T;T
Polyphen		0.92	P;P
Vest4		0.54
MutPred		0.31		Gain of relative solvent accessibility (P = 0.0275);Gain of relative solvent accessibility (P = 0.0275);
MVP		0.35
MPC		0.89
ClinPred		0.69	D
GERP RS		5.9
Varity_R		0.18
gMVP		0.26

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: chr1-91403144;