chr14-104586496-G-C

Position:

• chr14-104586496-G-C

Variant summary

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

The NM_001008404.3(C14orf180):​c.66G>C​(p.Lys22Asn) 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. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C14orf180 NM_001008404.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.143

Genes affected

C14orf180 (HGNC:33795): (chromosome 14 open reading frame 180) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM179 (HGNC:20137): (transmembrane protein 179) Predicted to be integral component of membrane. [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=0.07553828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C14orf180	NM_001008404.3	c.66G>C	p.Lys22Asn	missense_variant	2/5	ENST00000557649.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C14orf180	ENST00000557649.6	c.66G>C	p.Lys22Asn	missense_variant	2/5	1	NM_001008404.3	P1
C14orf180	ENST00000410013.1	c.66G>C	p.Lys22Asn	missense_variant	2/5	1		P1
C14orf180	ENST00000331952.6	c.66G>C	p.Lys22Asn	missense_variant	2/5	2
TMEM179	ENST00000415614.6	c.522+8669C>G		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.66G>C (p.K22N) alteration is located in exon 2 (coding exon 1) of the C14orf180 gene. This alteration results from a G to C substitution at nucleotide position 66, causing the lysine (K) at amino acid position 22 to be replaced by an asparagine (N). 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	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Uncertain	0.98
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Uncertain	-2.4	N;D;N
REVEL	Benign	0.048
Sift	Benign	0.060	T;D;T
Sift4G	Benign	0.075	T;D;T
Vest4		0.12
MutPred		0.10		Loss of methylation at K22 (P = 0.0069);Loss of methylation at K22 (P = 0.0069);Loss of methylation at K22 (P = 0.0069);
MVP		0.014
MPC		0.015
ClinPred		0.38	T
GERP RS		2.3
gMVP		0.027

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: chr14-105052833;