chr19-1854536-T-G

Variant names:

• chr19-1854536-T-G
• NM_031918.4:c.682A>C

Variant summary

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

The NM_031918.4(KLF16):​c.682A>C​(p.Ser228Arg) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLF16 NM_031918.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.480

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=0.12967277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF16	NM_031918.4	c.682A>C	p.Ser228Arg	missense_variant	Exon 2 of 2	ENST00000250916.6	NP_114124.1
KLF16	XM_047439498.1	c.652A>C	p.Ser218Arg	missense_variant	Exon 2 of 2		XP_047295454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF16	ENST00000250916.6	c.682A>C	p.Ser228Arg	missense_variant	Exon 2 of 2	1	NM_031918.4	ENSP00000250916.3
KLF16	ENST00000617223.1	c.682A>C	p.Ser228Arg	missense_variant	Exon 2 of 3	1		ENSP00000483701.1
KLF16	ENST00000541015.5	n.682A>C		non_coding_transcript_exon_variant	Exon 2 of 3	1		ENSP00000439973.1
KLF16	ENST00000592313.1	c.271A>C	p.Ser91Arg	missense_variant	Exon 2 of 2	3		ENSP00000480570.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.682A>C (p.S228R) alteration is located in exon 2 (coding exon 2) of the KLF16 gene. This alteration results from a A to C substitution at nucleotide position 682, causing the serine (S) at amino acid position 228 to be replaced by an arginine (R). 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T;T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.54	.;T;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.3	N;.;.
REVEL	Benign	0.045
Sift	Benign	0.52	T;.;.
Sift4G	Benign	0.32	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.046
MutPred		0.24		Loss of phosphorylation at S228 (P = 0.0064);Loss of phosphorylation at S228 (P = 0.0064);.;
MVP		0.25
MPC		2.4
ClinPred		0.63	D
GERP RS		3.3
Varity_R		0.19
gMVP		0.46

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: chr19-1854535;