chr19-1863140-G-A

Variant names:

• chr19-1863140-G-A
• rs768129357
• NM_031918.4:c.358C>T

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.358C>T​(p.Pro120Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 1,180,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P120A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLF16 NM_031918.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• 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=0.15061328).

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.358C>T	p.Pro120Ser	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.358C>T	p.Pro120Ser	missense	Exon 1 of 2	ENSP00000250916.3	Q9BXK1
	KLF16	ENST00000617223.1	TSL:1	c.358C>T	p.Pro120Ser	missense	Exon 1 of 3	ENSP00000483701.1	Q9BXK1
	KLF16	ENST00000541015.5	TSL:1	n.358C>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000439973.1	Q9BXK1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 147246 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000169 AC: 2 AN: 1180360 Hom.: 0 Cov.: 31 AF XY: 0.00000172 AC XY: 1 AN XY: 580032

African (AFR) AF: 0.00 AC: 0 AN: 23466

American (AMR) AF: 0.00 AC: 0 AN: 19072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17912

East Asian (EAS) AF: 0.00 AC: 0 AN: 23356

South Asian (SAS) AF: 0.00 AC: 0 AN: 54758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3098

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 954996

Other (OTH) AF: 0.0000223 AC: 1 AN: 44858

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 147246 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 71754

African (AFR) AF: 0.00 AC: 0 AN: 40748

American (AMR) AF: 0.00 AC: 0 AN: 14902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 5088

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66256

Other (OTH) AF: 0.00 AC: 0 AN: 2018

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.31	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	0.050	D
MutationAssessor	Benign	0.55	N
PhyloP100		1.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.13
Sift	Benign	0.069	T
Sift4G	Benign	0.083	T
Polyphen		0.053	B
Vest4		0.15
MutPred		0.25		Gain of phosphorylation at P120 (P = 0.0067)
MVP		0.81
MPC		1.3
ClinPred		0.060	T
GERP RS		-0.71
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.29
Mutation Taster		=96/4	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: rs768129357; hg19: chr19-1863139;