Variant 15-92630320-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207446.3(FAM174B):c.370C>T(p.Arg124Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,613,182 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

FAM174B
NM_207446.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM174B	NM_207446.3 linkuse as main transcript	c.370C>T	p.Arg124Cys	missense_variant	2/3	ENST00000327355.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM174B	ENST00000327355.6 linkuse as main transcript	c.370C>T	p.Arg124Cys	missense_variant	2/3	1	NM_207446.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000129

AC:

AN:

248200

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

134698

show subpopulations

Gnomad AFR exome

AF:

0.000390

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000838

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461046

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000105

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000650

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.000149

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 29, 2024

The c.370C>T (p.R124C) alteration is located in exon 2 (coding exon 2) of the FAM174B gene. This alteration results from a C to T substitution at nucleotide position 370, causing the arginine (R) at amino acid position 124 to be replaced by a cysteine (C). 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

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.61

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-7.6

REVEL

Uncertain

0.60

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.96

MVP

0.50

MPC

1.4

ClinPred

0.31

GERP RS

5.4

Varity_R

0.70

gMVP

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over