Genetic Variant NM_207446.3:c.301T>G (chr15-92655359-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.301T>G(p.Phe101Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000881 in 1,588,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. F101L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

FAM174B
NM_207446.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.642

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=0.20914176).

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.301T>G	p.Phe101Val	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.301T>G	p.Phe101Val	missense	Exon 1 of 3	ENSP00000329040.5	Q3ZCQ3
FAM174B	ENST00000896008.1		c.301T>G	p.Phe101Val	missense	Exon 1 of 2	ENSP00000566067.1
FAM174B	ENST00000555748.5	TSL:3	c.-309T>G		5_prime_UTR	Exon 1 of 3	ENSP00000452295.1	G3V5D1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

209250

AF XY:

0.0000259

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:

0.0000521

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000905

AC:

AN:

1436676

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

714874

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30828

American (AMR)

AF:

0.00

AC:

AN:

42592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25348

East Asian (EAS)

AF:

0.00

AC:

AN:

36038

South Asian (SAS)

AF:

0.00

AC:

AN:

83628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00000273

AC:

AN:

1100402

Other (OTH)

AF:

0.000169

AC:

AN:

59340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

Benign

0.17

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.012

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.61

M_CAP

Benign

0.063

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

0.64

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.7

REVEL

Benign

0.094

Sift

Benign

0.23

Sift4G

Benign

0.081

Polyphen

0.82

Vest4

0.41

MutPred

0.58

Loss of helix (P = 0.0795)

MVP

0.048

MPC

0.61

ClinPred

0.22

GERP RS

0.36

PromoterAI

0.018

Neutral

(source)

Varity_R

0.095

gMVP

0.42

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over