19-1863082-T-A

Variant names:

• chr19-1863082-T-A
• NM_031918.4:c.416A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031918.4(KLF16):​c.416A>T​(p.Tyr139Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,262,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: KLF16 NM_031918.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32582805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF16	NM_031918.4	c.416A>T	p.Tyr139Phe	missense_variant	Exon 1 of 2	ENST00000250916.6	NP_114124.1
KLF16	XM_047439498.1	c.428-8322A>T		intron_variant	Intron 1 of 1		XP_047295454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF16	ENST00000250916.6	c.416A>T	p.Tyr139Phe	missense_variant	Exon 1 of 2	1	NM_031918.4	ENSP00000250916.3
KLF16	ENST00000617223.1	c.416A>T	p.Tyr139Phe	missense_variant	Exon 1 of 3	1		ENSP00000483701.1
KLF16	ENST00000541015.5	n.416A>T		non_coding_transcript_exon_variant	Exon 1 of 3	1		ENSP00000439973.1
KLF16	ENST00000592313.1	c.-243A>T		upstream_gene_variant		3		ENSP00000480570.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1262580 Hom.: 0 Cov.: 31 AF XY: 0.00000160 AC XY: 1 AN XY: 625552

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000200

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.0032	T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Uncertain	0.90	.;D
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Uncertain	-0.037	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.7	N;.
REVEL	Uncertain	0.34
Sift	Benign	0.28	T;.
Sift4G	Benign	0.58	T;T
Polyphen		0.98	D;D
Vest4		0.10
MutPred		0.27		Gain of methylation at K140 (P = 0.0287);Gain of methylation at K140 (P = 0.0287);
MVP		0.97
MPC		1.5
ClinPred		0.51	D
GERP RS		0.14
Varity_R		0.20
gMVP		0.27

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: chr19-1863081;