NM_175900.4:c.280G>C

Variant names:

• chr16-29744672-C-G
• rs1341344153
• NM_175900.4:c.280G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175900.4(C16orf54):​c.280G>C​(p.Asp94His) 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. 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. D94N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C16orf54 NM_175900.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 0 publications found

Genes affected

C16orf54 (HGNC:26649): (chromosome 16 open reading frame 54) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33386064).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175900.4. 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
	C16orf54	NM_175900.4	MANE Select	c.280G>C	p.Asp94His	missense	Exon 2 of 2	NP_787096.2	Q6UWD8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C16orf54	ENST00000329410.4	TSL:1 MANE Select	c.280G>C	p.Asp94His	missense	Exon 2 of 2	ENSP00000327506.3	Q6UWD8
	C16orf54	ENST00000961953.1		c.280G>C	p.Asp94His	missense	Exon 2 of 2	ENSP00000632012.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.7
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.29		Loss of stability (P = 0.0634)
MVP		0.52
MPC		1.3
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.85
gMVP		0.30
Mutation Taster		=92/8	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: rs1341344153; hg19: chr16-29755993;