16-5058502-C-G

Variant names:

• chr16-5058502-C-G
• rs1956554106
• NM_001098514.3:c.618G>C
• C16orf89 p.Trp206Cys

Variant summary

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

The NM_001098514.3(C16orf89):​c.618G>C​(p.Trp206Cys) 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. 13/21 in silico tools predict 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: 32)
• Consequence: C16orf89 NM_001098514.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 0 publications found

Genes affected

C16orf89 (HGNC:28687): (chromosome 16 open reading frame 89) This gene is expressed predominantly in the thyroid. Based on expression patterns similar to thyroid transcription factors and proteins, this gene may function in the development and function of the thyroid. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ALG1 (HGNC:18294): (ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase) The enzyme encoded by this gene catalyzes the first mannosylation step in the biosynthesis of lipid-linked oligosaccharides. This gene is mutated in congenital disorder of glycosylation type Ik. [provided by RefSeq, Dec 2008]

ALG1 Gene-Disease associations (from GenCC):

• ALG1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

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=0.32896417).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098514.3. 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
	C16orf89	NM_001098514.3	MANE Select	c.618G>C	p.Trp206Cys	missense	Exon 4 of 8	NP_001091984.2	Q6UX73-2
	C16orf89	NM_152459.5		c.618G>C	p.Trp206Cys	missense	Exon 4 of 8	NP_689672.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C16orf89	ENST00000472572.8	TSL:1 MANE Select	c.618G>C	p.Trp206Cys	missense	Exon 4 of 8	ENSP00000420566.2	Q6UX73-2
	C16orf89	ENST00000474471.7	TSL:5	c.618G>C	p.Trp206Cys	missense	Exon 4 of 9	ENSP00000417158.3	A0A0A0MT71
	C16orf89	ENST00000315997.5	TSL:1	c.618G>C	p.Trp206Cys	missense	Exon 4 of 8	ENSP00000324672.5	Q6UX73-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.31
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.15
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.0080	D
Varity_R		0.14
gMVP		0.60

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1956554106;

hg19: chr16-5108503;