rs3746045

chr19-1854558-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031918.4(KLF16):c.660T>C(p.Pro220=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,567,310 control chromosomes in the GnomAD database, including 59,909 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (11920 hom., cov: 33)
  • Exomes 𝑓: 0.25 (47989 hom.)
• Consequence: KLF16 NM_031918.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.83

Genes affected

KLF16 (HGNC:16857): (KLF transcription factor 16) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within dopamine receptor signaling pathway. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-3.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF16	NM_031918.4	c.660T>C	p.Pro220=	synonymous_variant	2/2	ENST00000250916.6
KLF16	XM_047439498.1	c.630T>C	p.Pro210=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF16	ENST00000250916.6	c.660T>C	p.Pro220=	synonymous_variant	2/2	1	NM_031918.4	P1
KLF16	ENST00000617223.1	c.660T>C	p.Pro220=	synonymous_variant	2/3	1		P1
KLF16	ENST00000541015.5	c.660T>C	p.Pro220=	synonymous_variant, NMD_transcript_variant	2/3	1
KLF16	ENST00000592313.1	c.249T>C	p.Pro83=	synonymous_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54352 AN: 151654 Hom.: 11898 Cov.: 33

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.317

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.342

GnomAD3 exomes AF: 0.298 AC: 54480 AN: 182616 Hom.: 9168 AF XY: 0.287 AC XY: 29073 AN XY: 101126

Gnomad AFR exome AF: 0.609

Gnomad AMR exome AF: 0.407

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.388

Gnomad SAS exome AF: 0.291

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.275

GnomAD4 exome AF: 0.247 AC: 349833 AN: 1415540 Hom.: 47989 Cov.: 35 AF XY: 0.248 AC XY: 174041 AN XY: 702488

Gnomad4 AFR exome AF: 0.635

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.270

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.359 AC: 54417 AN: 151770 Hom.: 11920 Cov.: 33 AF XY: 0.358 AC XY: 26520 AN XY: 74164

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.341

Alfa AF: 0.286 Hom.: 1399

Bravo AF: 0.383

Asia WGS AF: 0.365 AC: 1268 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.18
Dann	Benign	0.40

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: rs3746045; hg19: chr19-1854557; COSMIC: COSV51736124; COSMIC: COSV51736124;