Genetic Variant C16orf78:p.Ser88Phe (chr16-49377843-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144602.4(C16orf78):c.263C>T(p.Ser88Phe) 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. 14/21 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

C16orf78
NM_144602.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.299

Publications

0 publications found

Variant links:

Genes affected

C16orf78 (HGNC:28479): (chromosome 16 open reading frame 78) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

C16orf78 links:

ENSG00000262950 (HGNC:):

ENSG00000262950 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08301085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C16orf78	NM_144602.4 link	c.263C>T	p.Ser88Phe	missense_variant	Exon 2 of 5	ENST00000299191.4	NP_653203.1	Q8WTQ4
LOC105371244	XR_001752167.2 link	n.1813-2913G>A		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C16orf78	ENST00000299191.4 link	c.263C>T	p.Ser88Phe	missense_variant	Exon 2 of 5	1	NM_144602.4	ENSP00000299191.3		Q8WTQ4
ENSG00000262950	ENST00000849660.1 link	n.586-12198G>A		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

184108

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1421532

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702876

African (AFR)

AF:

0.00

AC:

AN:

32870

American (AMR)

AF:

0.00

AC:

AN:

38944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25302

East Asian (EAS)

AF:

0.00

AC:

AN:

38230

South Asian (SAS)

AF:

0.00

AC:

AN:

80944

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5200

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090424

Other (OTH)

AF:

0.00

AC:

AN:

58838

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 30, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.263C>T (p.S88F) alteration is located in exon 2 (coding exon 2) of the C16orf78 gene. This alteration results from a C to T substitution at nucleotide position 263, causing the serine (S) at amino acid position 88 to be replaced by a phenylalanine (F). 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

0.14

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.5

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.39

M_CAP

Benign

0.0033

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

-0.30

PROVEAN

Benign

-1.8

REVEL

Benign

0.020

Sift

Uncertain

0.027

Sift4G

Uncertain

0.052

Polyphen

0.0

Vest4

0.086

MutPred

0.26

Loss of phosphorylation at S88 (P = 0.0284);

MVP

0.040

MPC

0.020

ClinPred

0.051

GERP RS

-0.49

Varity_R

0.058

gMVP

0.010

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over