Genetic Variant C16orf74:p.Val27Phe (chr16-85710257-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_206967.3(C16orf74):c.79G>T(p.Val27Phe) 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. V27I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

C16orf74
NM_206967.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

Publications

0 publications found

Variant links:

Genes affected

C16orf74 (HGNC:23362): (chromosome 16 open reading frame 74)

C16orf74 links:

ENSG00000287125 (HGNC:):

ENSG00000287125 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.30511278).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206967.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C16orf74	NM_206967.3	MANE Select	c.79G>T	p.Val27Phe	missense	Exon 3 of 4	NP_996850.1	Q96GX8-1
C16orf74	NR_161452.1		n.310G>T		non_coding_transcript_exon	Exon 4 of 5
C16orf74	NR_161454.1		n.246G>T		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C16orf74	ENST00000284245.9	TSL:1 MANE Select	c.79G>T	p.Val27Phe	missense	Exon 3 of 4	ENSP00000284245.3	Q96GX8-1
C16orf74	ENST00000602583.5	TSL:1	c.43G>T	p.Val15Phe	missense	Exon 1 of 2	ENSP00000473536.1	Q96GX8-2
C16orf74	ENST00000602675.5	TSL:1	c.-63G>T		5_prime_UTR	Exon 3 of 4	ENSP00000473306.1	R4GMV5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000744

AC:

AN:

134332

AF XY:

0.00

show subpopulations

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:

0.0000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1361012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

673656

African (AFR)

AF:

0.00

AC:

AN:

27322

American (AMR)

AF:

0.00

AC:

AN:

24428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23320

East Asian (EAS)

AF:

0.00

AC:

AN:

32336

South Asian (SAS)

AF:

0.00

AC:

AN:

70210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074314

Other (OTH)

AF:

0.00

AC:

AN:

56492

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.79

M_CAP

Benign

0.064

MetaRNN

Benign

0.31

MetaSVM

Uncertain

0.00040

PhyloP100

1.4

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.30

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.43

MutPred

0.16

Loss of disorder (P = 0.1639)

MVP

0.16

MPC

0.011

ClinPred

0.99

GERP RS

4.8

Varity_R

0.45

gMVP

0.18

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over