chr19-20545971-A-C

Variant names:

• chr19-20545971-A-C
• rs7254995
• NM_001159293.2:c.232T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001159293.2(ZNF737):​c.232T>G​(p.Cys78Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 1,540,878 control chromosomes in the GnomAD database, including 2,444 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.065 (395 hom., cov: 33)
  • Exomes 𝑓: 0.051 (2049 hom.)
• Consequence: ZNF737 NM_001159293.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.892
• Publications: 12 publications found

Genes affected

ZNF737 (HGNC:32468): (zinc finger protein 737) 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]

ENSG00000269043 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028956234).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159293.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF737	NM_001159293.2	MANE Select	c.232T>G	p.Cys78Gly	missense	Exon 4 of 4	NP_001152765.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF737	ENST00000427401.9	TSL:2 MANE Select	c.232T>G	p.Cys78Gly	missense	Exon 4 of 4	ENSP00000395733.3
	ZNF737	ENST00000594419.1	TSL:3	c.40T>G	p.Cys14Gly	missense	Exon 3 of 3	ENSP00000471784.1
	ZNF737	ENST00000597940.1	TSL:5	n.*198T>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000470737.1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9883 AN: 152154 Hom.: 396 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0362

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0758

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0525

Gnomad OTH AF: 0.0583

GnomAD2 exomes AF: 0.0498 AC: 9335 AN: 187382 AF XY: 0.0488

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.0243

Gnomad ASJ exome AF: 0.0424

Gnomad EAS exome AF: 0.000250

Gnomad FIN exome AF: 0.0739

Gnomad NFE exome AF: 0.0525

Gnomad OTH exome AF: 0.0438

GnomAD4 exome AF: 0.0507 AC: 70421 AN: 1388608 Hom.: 2049 Cov.: 33 AF XY: 0.0500 AC XY: 34248 AN XY: 685118

African (AFR) AF: 0.114 AC: 3475 AN: 30580

American (AMR) AF: 0.0247 AC: 746 AN: 30254

Ashkenazi Jewish (ASJ) AF: 0.0376 AC: 790 AN: 21012

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39246

South Asian (SAS) AF: 0.0375 AC: 2701 AN: 72022

European-Finnish (FIN) AF: 0.0716 AC: 3619 AN: 50520

Middle Eastern (MID) AF: 0.0380 AC: 206 AN: 5416

European-Non Finnish (NFE) AF: 0.0518 AC: 56067 AN: 1082342

Other (OTH) AF: 0.0491 AC: 2812 AN: 57216

GnomAD4 genome AF: 0.0650 AC: 9897 AN: 152270 Hom.: 395 Cov.: 33 AF XY: 0.0651 AC XY: 4847 AN XY: 74458

African (AFR) AF: 0.108 AC: 4478 AN: 41542

American (AMR) AF: 0.0361 AC: 553 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 141 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0373 AC: 180 AN: 4828

European-Finnish (FIN) AF: 0.0758 AC: 804 AN: 10610

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0525 AC: 3574 AN: 68012

Other (OTH) AF: 0.0577 AC: 122 AN: 2114

Alfa AF: 0.0518 Hom.: 925

Bravo AF: 0.0637

TwinsUK AF: 0.0445 AC: 165

ALSPAC AF: 0.0550 AC: 212

ESP6500AA AF: 0.104 AC: 144

ESP6500EA AF: 0.0553 AC: 176

ExAC AF: 0.0484 AC: 5847

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.63
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.89
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-10	D
REVEL	Benign	0.028
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.036	D
Vest4		0.049
MPC		0.0040
ClinPred		0.079	T
GERP RS		-0.57
Varity_R		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7254995; hg19: chr19-20728777; COSMIC: COSV71199614; COSMIC: COSV71199614;