chr14-44905461-C-A

Variant names:

• chr14-44905461-C-A
• NM_001017923.2:c.844C>A

Variant summary

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

The NM_001017923.2(C14orf28):​c.844C>A​(p.Leu282Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000706 in 1,416,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: C14orf28 NM_001017923.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69

Genes affected

C14orf28 (HGNC:19834): (chromosome 14 open reading frame 28)

ENSG00000258949 (HGNC:):

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=0.34215498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C14orf28	NM_001017923.2	c.844C>A	p.Leu282Ile	missense_variant	Exon 5 of 5	ENST00000325192.8	NP_001017923.1
C14orf28	XM_011536408.1	c.364C>A	p.Leu122Ile	missense_variant	Exon 4 of 4		XP_011534710.1
LOC101927418	NR_110050.1	n.162-6148G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C14orf28	ENST00000325192.8	c.844C>A	p.Leu282Ile	missense_variant	Exon 5 of 5	1	NM_001017923.2	ENSP00000326846.3
C14orf28	ENST00000557112.1	c.754C>A	p.Leu252Ile	missense_variant	Exon 4 of 4	5		ENSP00000451791.1
C14orf28	ENST00000555826.5	n.1703C>A		non_coding_transcript_exon_variant	Exon 3 of 3	2
ENSG00000258949	ENST00000555157.1	n.108-6148G>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416992 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 704168

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: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.90	L;.
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;.
Vest4		0.53
MutPred		0.26		Gain of catalytic residue at M277 (P = 0.0012);.;
MVP		0.14
MPC		0.25
ClinPred		0.87	D
GERP RS		5.0
Varity_R		0.59
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: chr14-45374664;