19-1863133-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.414

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 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/exons	MANE	UniProt
KLF16	NM_031918.4	c.365C>T	p.Ala122Val	missense_variant	1/2	ENST00000250916.6
KLF16	XM_047439498.1	c.428-8373C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF16	ENST00000250916.6	c.365C>T	p.Ala122Val	missense_variant	1/2	1	NM_031918.4	P1
KLF16	ENST00000617223.1	c.365C>T	p.Ala122Val	missense_variant	1/3	1		P1
KLF16	ENST00000541015.5	c.365C>T	p.Ala122Val	missense_variant, NMD_transcript_variant	1/3	1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000336 AC: 4 AN: 1189534 Hom.: 0 Cov.: 31 AF XY: 0.00000513 AC XY: 3 AN XY: 585294

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.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2021

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	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	20
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0094	T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.042	N
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.82	D
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	T
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.

Other links and lift over

hg19: chr19-1863132;