Variant 15-92655467-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_207446.3(FAM174B):c.193A>G(p.Ser65Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000356 in 1,404,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

FAM174B
NM_207446.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.382

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029642552).

BP6

Variant 15-92655467-T-C is Benign according to our data. Variant chr15-92655467-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2346505.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM174B	NM_207446.3 linkuse as main transcript	c.193A>G	p.Ser65Gly	missense_variant	1/3	ENST00000327355.6	NP_997329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FAM174B	ENST00000327355.6 linkuse as main transcript	c.193A>G	p.Ser65Gly	missense_variant	1/3	1	NM_207446.3	ENSP00000329040	P1
FAM174B	ENST00000556824.5 linkuse as main transcript	c.-81+1055A>G		intron_variant		5		ENSP00000455517
FAM174B	ENST00000557398.2 linkuse as main transcript	c.-89-25122A>G		intron_variant		4		ENSP00000456099
FAM174B	ENST00000557480.5 linkuse as main transcript	c.-81+12431A>G		intron_variant		4		ENSP00000455213

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000693

AC:

AN:

144294

Hom.:

AF XY:

0.00

AC XY:

AN XY:

80784

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000356

AC:

AN:

1404954

Hom.:

Cov.:

AF XY:

0.00000431

AC XY:

AN XY:

695292

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000276

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000865

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.38

DEOGEN2

Benign

0.0059

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.22

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.2

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.51

REVEL

Benign

0.043

Sift

Benign

0.64

Sift4G

Benign

0.95

Polyphen

0.0

Vest4

0.072

MutPred

0.29

Loss of glycosylation at S65 (P = 4e-04);

MVP

0.014

MPC

0.34

ClinPred

0.012

GERP RS

2.0

Varity_R

0.047

gMVP

0.22

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