Variant chr22-45323197-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017911.4(FAM118A):c.70C>T(p.Arg24Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,611,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

FAM118A
NM_017911.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37

Variant links:

Genes affected

FAM118A (HGNC:1313): (family with sequence similarity 118 member A) Enables identical protein binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM118A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1454772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM118A	NM_017911.4 linkuse as main transcript	c.70C>T	p.Arg24Trp	missense_variant	3/9	ENST00000441876.7	NP_060381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM118A	ENST00000441876.7 linkuse as main transcript	c.70C>T	p.Arg24Trp	missense_variant	3/9	1	NM_017911.4	ENSP00000395892	P1	Q9NWS6-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000799

AC:

AN:

250384

Hom.:

AF XY:

0.0000812

AC XY:

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000343

AC:

AN:

1459544

Hom.:

Cov.:

AF XY:

0.0000372

AC XY:

AN XY:

725488

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000995

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000161

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000741

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

Mar 07, 2024

The c.70C>T (p.R24W) alteration is located in exon 4 (coding exon 2) of the FAM118A gene. This alteration results from a C to T substitution at nucleotide position 70, causing the arginine (R) at amino acid position 24 to be replaced by a tryptophan (W). 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

0.22

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

.;D;D;D

M_CAP

Benign

0.037

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

L;L;.;.

MutationTaster

Benign

0.61

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.5

D;D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.013

D;D;D;D

Sift4G

Uncertain

0.011

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.54

MutPred

0.35

Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);

MVP

0.13

MPC

0.66

ClinPred

0.50

GERP RS

-0.15

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.12

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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