rs17131242

chr1-90939688-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_201269.3(ZNF644):c.1666A>G(p.Met556Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,614,022 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.013 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (45 hom.)
• Consequence: ZNF644 NM_201269.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.376

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017351508).
• BP6: Variant 1-90939688-T-C is Benign according to our data. Variant chr1-90939688-T-C is described in ClinVar as [Benign]. Clinvar id is 780248.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1930/152262) while in subpopulation AFR AF= 0.0438 (1819/41574). AF 95% confidence interval is 0.0421. There are 39 homozygotes in gnomad4. There are 921 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1923 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF644	NM_201269.3	c.1666A>G	p.Met556Val	missense_variant	3/6	ENST00000337393.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF644	ENST00000337393.10	c.1666A>G	p.Met556Val	missense_variant	3/6	1	NM_201269.3	P1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1923 AN: 152144 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0101

GnomAD3 exomes AF: 0.00343 AC: 858 AN: 250042 Hom.: 22 AF XY: 0.00249 AC XY: 337 AN XY: 135140

Gnomad AFR exome AF: 0.0460

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000599

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000977

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00135 AC: 1978 AN: 1461760 Hom.: 45 Cov.: 33 AF XY: 0.00113 AC XY: 819 AN XY: 727166

Gnomad4 AFR exome AF: 0.0466

Gnomad4 AMR exome AF: 0.00239

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000935

Gnomad4 OTH exome AF: 0.00270

GnomAD4 genome AF: 0.0127 AC: 1930 AN: 152262 Hom.: 39 Cov.: 32 AF XY: 0.0124 AC XY: 921 AN XY: 74478

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00996

Alfa AF: 0.00227 Hom.: 13

Bravo AF: 0.0148

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0399 AC: 176

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00399 AC: 484

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.0080
Dann	Benign	0.20
DEOGEN2	Benign	0.0035	T;T;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.049	N
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.070	N;N;.
REVEL	Benign	0.012
Sift	Benign	0.82	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.097
MVP		0.12
MPC		0.24
ClinPred		0.00082	T
GERP RS		-4.2
Varity_R		0.027
gMVP		0.34

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: rs17131242; hg19: chr1-91405245; COSMIC: COSV61350853; COSMIC: COSV61350853;