Genetic Variant NM_207446.3:c.303T>G (chr15-92655357-A-C) – 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_207446.3(FAM174B):c.303T>G(p.Phe101Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000627 in 1,436,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F101V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

FAM174B
NM_207446.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Publications

0 publications found

Variant links:

Genes affected

FAM174B (HGNC:34339): (family with sequence similarity 174 member B) Involved in Golgi organization. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM174B 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=0.10485798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207446.3. 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
	FAM174B	NM_207446.3	MANE Select	c.303T>G	p.Phe101Leu	missense	Exon 1 of 3	NP_997329.2	Q3ZCQ3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM174B	ENST00000327355.6	TSL:1 MANE Select	c.303T>G	p.Phe101Leu	missense	Exon 1 of 3	ENSP00000329040.5	Q3ZCQ3
FAM174B	ENST00000555748.5	TSL:3	c.-307T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000452295.1	G3V5D1
FAM174B	ENST00000896008.1		c.303T>G	p.Phe101Leu	missense	Exon 1 of 2	ENSP00000566067.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000627

AC:

AN:

1436550

Hom.:

Cov.:

AF XY:

0.00000979

AC XY:

AN XY:

714772

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30822

American (AMR)

AF:

0.00

AC:

AN:

42598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25344

East Asian (EAS)

AF:

0.00

AC:

AN:

36024

South Asian (SAS)

AF:

0.00

AC:

AN:

83654

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00000727

AC:

AN:

1100294

Other (OTH)

AF:

0.0000169

AC:

AN:

59316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0064

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.56

M_CAP

Benign

0.036

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

1.8

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.20

REVEL

Benign

0.075

Sift

Benign

0.67

Sift4G

Benign

1.0

Polyphen

0.049

Vest4

0.25

MutPred

0.58

Loss of MoRF binding (P = 0.1919)

MVP

0.014

MPC

0.44

ClinPred

0.41

GERP RS

3.1

PromoterAI

0.023

Neutral

(source)

Varity_R

0.11

gMVP

0.34

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over