dbSNP rs3746045: KLF16:p.Pro220Pro (chr19-1854558-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_031918.4(KLF16):c.660T>C(p.Pro220Pro) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.83

Variant links:

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]

KLF16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KLF16	NM_031918.4 link	c.660T>C	p.Pro220Pro	synonymous_variant	Exon 2 of 2	ENST00000250916.6	NP_114124.1	Q9BXK1
KLF16	XM_047439498.1 link	c.630T>C	p.Pro210Pro	synonymous_variant	Exon 2 of 2		XP_047295454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KLF16	ENST00000250916.6 link	c.660T>C	p.Pro220Pro	synonymous_variant	Exon 2 of 2	1	NM_031918.4	ENSP00000250916.3	Q9BXK1
KLF16	ENST00000617223.1 link	c.660T>C	p.Pro220Pro	synonymous_variant	Exon 2 of 3	1		ENSP00000483701.1	Q9BXK1
KLF16	ENST00000541015.5 link	n.660T>C		non_coding_transcript_exon_variant	Exon 2 of 3	1		ENSP00000439973.1	Q9BXK1
KLF16	ENST00000592313.1 link	c.249T>C	p.Pro83Pro	synonymous_variant	Exon 2 of 2	3		ENSP00000480570.1	A0A087WWX5

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54352

AN:

151654

Hom.:

11898

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.298

AC:

54480

AN:

182616

AF XY:

0.287

show subpopulations

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 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.:

AF XY:

0.248

AC XY:

174041

AN XY:

702488

show subpopulations

Gnomad4 AFR exome

AF:

0.635

AC:

20297

AN:

31960

Gnomad4 AMR exome

AF:

0.408

AC:

16120

AN:

39468

Gnomad4 ASJ exome

AF:

0.270

AC:

6844

AN:

25370

Gnomad4 EAS exome

AF:

0.448

AC:

16775

AN:

37456

Gnomad4 SAS exome

AF:

0.290

AC:

24148

AN:

83240

Gnomad4 FIN exome

AF:

0.199

AC:

7432

AN:

37432

Gnomad4 NFE exome

AF:

0.220

AC:

240806

AN:

1096980

Gnomad4 Remaining exome

AF:

0.270

AC:

15851

AN:

58798

Heterozygous variant carriers

14335

28670

43004

57339

71674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

8696

17392

26088

34784

43480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.359

AC:

54417

AN:

151770

Hom.:

11920

Cov.:

AF XY:

0.358

AC XY:

26520

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.609

AC:

0.608753

AN:

0.608753

Gnomad4 AMR

AF:

0.399

AC:

0.399489

AN:

0.399489

Gnomad4 ASJ

AF:

0.271

AC:

0.270629

AN:

0.270629

Gnomad4 EAS

AF:

0.413

AC:

0.412795

AN:

0.412795

Gnomad4 SAS

AF:

0.307

AC:

0.306908

AN:

0.306908

Gnomad4 FIN

AF:

0.211

AC:

0.211357

AN:

0.211357

Gnomad4 NFE

AF:

0.225

AC:

0.224815

AN:

0.224815

Gnomad4 OTH

AF:

0.341

AC:

0.340779

AN:

0.340779

Heterozygous variant carriers

1670

3341

5011

6682

8352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over