chr19-20545971-A-C

Position:

• chr19-20545971-A-C

Variant summary

Our verdict is Benign. Variant got -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. 12/19 in silico tools predict 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. C78S) has been classified as Likely benign.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF737	NM_001159293.2	c.232T>G	p.Cys78Gly	missense_variant	4/4	ENST00000427401.9	NP_001152765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF737	ENST00000427401.9	c.232T>G	p.Cys78Gly	missense_variant	4/4	2	NM_001159293.2	ENSP00000395733.3

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

GnomAD3 exomes AF: 0.0498 AC: 9335 AN: 187382 Hom.: 294 AF XY: 0.0488 AC XY: 4891 AN XY: 100126

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 SAS exome AF: 0.0420

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

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0247

Gnomad4 ASJ exome AF: 0.0376

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.0375

Gnomad4 FIN exome AF: 0.0716

Gnomad4 NFE exome AF: 0.0518

Gnomad4 OTH exome AF: 0.0491

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

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0361

Gnomad4 ASJ AF: 0.0406

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0373

Gnomad4 FIN AF: 0.0758

Gnomad4 NFE AF: 0.0525

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0506 Hom.: 433

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 v4.3

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;D
MetaRNN	Benign	0.0029	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M;.
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

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