chr16-29744672-C-T

Variant names:

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

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>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
• 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=0.2855526).

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>A	p.Asp94Asn	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>A	p.Asp94Asn	missense	Exon 2 of 2	ENSP00000327506.3	Q6UWD8
	C16orf54	ENST00000961953.1		c.280G>A	p.Asp94Asn	missense	Exon 2 of 2	ENSP00000632012.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000989 AC: 1 AN: 101082 AF XY: 0.0000195

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000982

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28846

American (AMR) AF: 0.00 AC: 0 AN: 21822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18984

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35720

South Asian (SAS) AF: 0.00 AC: 0 AN: 63874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5194

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1044754

Other (OTH) AF: 0.00 AC: 0 AN: 54334

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.7
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

Other links and lift over

dbSNP: rs1341344153; hg19: chr16-29755993; COSMIC: COSV107342806; COSMIC: COSV107342806;