19-1863179-C-T

Variant names:

• chr19-1863179-C-T
• rs568223808
• NM_031918.4:c.319G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031918.4(KLF16):​c.319G>A​(p.Ala107Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. A107S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLF16 NM_031918.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0872283).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031918.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF16	NM_031918.4	MANE Select	c.319G>A	p.Ala107Thr	missense	Exon 1 of 2	NP_114124.1	Q9BXK1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF16	ENST00000250916.6	TSL:1 MANE Select	c.319G>A	p.Ala107Thr	missense	Exon 1 of 2	ENSP00000250916.3	Q9BXK1
	KLF16	ENST00000617223.1	TSL:1	c.319G>A	p.Ala107Thr	missense	Exon 1 of 3	ENSP00000483701.1	Q9BXK1
	KLF16	ENST00000541015.5	TSL:1	n.319G>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000439973.1	Q9BXK1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000280 AC: 3 AN: 1071602 Hom.: 0 Cov.: 31 AF XY: 0.00000579 AC XY: 3 AN XY: 517858

African (AFR) AF: 0.00 AC: 0 AN: 20722

American (AMR) AF: 0.00 AC: 0 AN: 9224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12778

East Asian (EAS) AF: 0.00 AC: 0 AN: 20728

South Asian (SAS) AF: 0.0000314 AC: 1 AN: 31896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2694

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 901090

Other (OTH) AF: 0.0000251 AC: 1 AN: 39906

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.29
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.034
Sift	Benign	0.55	T
Sift4G	Benign	0.31	T
Polyphen		0.75	P
Vest4		0.14
MutPred		0.31		Gain of glycosylation at A107 (P = 2e-04)
MVP		0.15
MPC		1.3
ClinPred		0.12	T
GERP RS		-0.25
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.041
gMVP		0.26
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs568223808; hg19: chr19-1863178;