chr14-44904481-C-G

Variant names:

• chr14-44904481-C-G
• rs76976586
• NM_001017923.2:c.701C>G

Variant summary

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

The NM_001017923.2(C14orf28):​c.701C>G​(p.Ser234Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,832 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C14orf28 NM_001017923.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

Genes affected

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

ENSG00000258949 (HGNC:):

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=0.2276757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C14orf28	NM_001017923.2	c.701C>G	p.Ser234Cys	missense_variant	Exon 4 of 5	ENST00000325192.8	NP_001017923.1
C14orf28	XM_011536408.1	c.221C>G	p.Ser74Cys	missense_variant	Exon 3 of 4		XP_011534710.1
LOC101927418	NR_110050.1	n.162-5168G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C14orf28	ENST00000325192.8	c.701C>G	p.Ser234Cys	missense_variant	Exon 4 of 5	1	NM_001017923.2	ENSP00000326846.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250210 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135252

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459832 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726108

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.088
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;.
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Benign	0.10
Sift	Benign	0.060	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0020	B;.
Vest4		0.50
MutPred		0.33		Gain of catalytic residue at Q230 (P = 0.0032);.;
MVP		0.32
MPC		0.050
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.38
gMVP		0.48

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: rs76976586; hg19: chr14-45373684;