chr16-29744672-C-T

Position:

• chr16-29744672-C-T

Variant summary

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

The NM_175900.4(C16orf54):​c.280G>A​(p.Asp94Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,320,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: C16orf54 NM_175900.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

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

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=0.2855526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C16orf54	NM_175900.4	c.280G>A	p.Asp94Asn	missense_variant	2/2	ENST00000329410.4
C16orf54	XM_047433977.1	c.337G>A	p.Asp113Asn	missense_variant	2/2
C16orf54	XM_047433978.1	c.310G>A	p.Asp104Asn	missense_variant	2/2
C16orf54	XM_047433979.1	c.337G>A	p.Asp113Asn	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C16orf54	ENST00000329410.4	c.280G>A	p.Asp94Asn	missense_variant	2/2	1	NM_175900.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1320236 Hom.: 0 Cov.: 31 AF XY: 0.00000156 AC XY: 1 AN XY: 642828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Oct 18, 2021

The c.280G>A (p.D94N) alteration is located in exon 2 (coding exon 1) of the C16orf54 gene. This alteration results from a G to A substitution at nucleotide position 280, causing the aspartic acid (D) at amino acid position 94 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	Benign	0.30
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.97	D
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.099	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.28		Gain of helix (P = 0.062);
MVP		0.31
MPC		1.1
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.74
gMVP		0.19

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: rs1341344153; hg19: chr16-29755993;