Variant chr15-92655458-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000327355.6(FAM174B):c.202T>G(p.Ser68Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 630,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

FAM174B
ENST00000327355.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0340

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053276032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM174B	NM_207446.3 linkuse as main transcript	c.202T>G	p.Ser68Ala	missense_variant	1/3	ENST00000327355.6	NP_997329.2	Q3ZCQ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM174B	ENST00000327355.6 linkuse as main transcript	c.202T>G	p.Ser68Ala	missense_variant	1/3	1	NM_207446.3	ENSP00000329040.5	Q3ZCQ3
FAM174B	ENST00000557480.5 linkuse as main transcript	c.-81+12440T>G		intron_variant		4		ENSP00000455213.1	H3BP98
FAM174B	ENST00000556824.5 linkuse as main transcript	c.-81+1064T>G		intron_variant		5		ENSP00000455517.1	H3BPY1
FAM174B	ENST00000557398.2 linkuse as main transcript	c.-89-25113T>G		intron_variant		4		ENSP00000456099.2	H3BR69

Frequencies

GnomAD3 genomes

AF:

0.000101

AC:

AN:

98974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

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:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000128

AC:

AN:

77992

Hom.:

AF XY:

0.000139

AC XY:

AN XY:

43046

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000236

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000327

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

101

AN:

531618

Hom.:

Cov.:

AF XY:

0.000192

AC XY:

AN XY:

276732

show subpopulations

Gnomad4 AFR exome

AF:

0.0000765

Gnomad4 AMR exome

AF:

0.0000631

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000453

Gnomad4 FIN exome

AF:

0.0000312

Gnomad4 NFE exome

AF:

0.000261

Gnomad4 OTH exome

AF:

0.0000370

GnomAD4 genome

AF:

0.000101

AC:

AN:

98974

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

47928

show subpopulations

Gnomad4 AFR

AF:

0.0000726

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000281

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

Aug 09, 2021

The c.202T>G (p.S68A) alteration is located in exon 1 (coding exon 1) of the FAM174B gene. This alteration results from a T to G substitution at nucleotide position 202, causing the serine (S) at amino acid position 68 to be replaced by an alanine (A). 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

0.077

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.16

M_CAP

Benign

0.020

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.16

REVEL

Benign

0.015

Sift

Benign

0.42

Sift4G

Benign

0.62

Polyphen

0.0030

Vest4

0.14

MVP

0.030

MPC

0.31

ClinPred

0.016

GERP RS

0.57

Varity_R

0.049

gMVP

0.23

Splicing

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