rs2012105914

Variant names:

• chr19-1863158-G-A
• rs2012105914
• NM_031918.4:c.340C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-1863158-G-A
• chr19-1863158-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031918.4(KLF16):​c.340C>T​(p.Arg114Cys) 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. 14/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLF16 NM_031918.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613

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=0.08816525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF16	NM_031918.4	c.340C>T	p.Arg114Cys	missense_variant	Exon 1 of 2	ENST00000250916.6	NP_114124.1
KLF16	XM_047439498.1	c.428-8398C>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.340C>T	p.Arg114Cys	missense_variant	Exon 1 of 2	1	NM_031918.4	ENSP00000250916.3
KLF16	ENST00000617223.1	c.340C>T	p.Arg114Cys	missense_variant	Exon 1 of 3	1		ENSP00000483701.1
KLF16	ENST00000541015.5	n.340C>T		non_coding_transcript_exon_variant	Exon 1 of 3	1		ENSP00000439973.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1150732 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 563872

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.47	.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.014
Sift	Benign	0.052	T;.
Sift4G	Uncertain	0.050	T;T
Polyphen		0.046	B;B
Vest4		0.092
MutPred		0.44		Loss of methylation at R114 (P = 0.002);Loss of methylation at R114 (P = 0.002);
MVP		0.12
MPC		1.7
ClinPred		0.13	T
GERP RS		0.0059
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.10
gMVP		0.34

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

Other links and lift over

dbSNP: rs2012105914; hg19: chr19-1863157;