Genetic Variant NM_031918.4:c.365C>T (chr19-1863133-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031918.4(KLF16):c.365C>T(p.Ala122Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000336 in 1,189,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

KLF16
NM_031918.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.414

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12947139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF16	NM_031918.4 link	c.365C>T	p.Ala122Val	missense_variant	Exon 1 of 2	ENST00000250916.6	NP_114124.1	Q9BXK1
KLF16	XM_047439498.1 link	c.428-8373C>T		intron_variant	Intron 1 of 1		XP_047295454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KLF16	ENST00000250916.6 link	c.365C>T	p.Ala122Val	missense_variant	Exon 1 of 2	1	NM_031918.4	ENSP00000250916.3	Q9BXK1
KLF16	ENST00000617223.1 link	c.365C>T	p.Ala122Val	missense_variant	Exon 1 of 3	1		ENSP00000483701.1	Q9BXK1
KLF16	ENST00000541015.5 link	n.365C>T		non_coding_transcript_exon_variant	Exon 1 of 3	1		ENSP00000439973.1	Q9BXK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000336

AC:

AN:

1189534

Hom.:

Cov.:

AF XY:

0.00000513

AC XY:

AN XY:

585294

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000353

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000208

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 30, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.365C>T (p.A122V) alteration is located in exon 1 (coding exon 1) of the KLF16 gene. This alteration results from a C to T substitution at nucleotide position 365, causing the alanine (A) at amino acid position 122 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0094

T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.27

.;T

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.69

N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.91

N;.

REVEL

Benign

0.13

Sift

Benign

0.11

T;.

Sift4G

Benign

0.14

T;T

Polyphen

0.12

B;B

Vest4

0.087

MutPred

0.37

Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);

MVP

0.82

MPC

1.3

ClinPred

0.097

GERP RS

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

Varity_R

0.064

gMVP

0.26

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over