rs6007594

chr22-45332489-G-Achr22-45332489-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017911.4(FAM118A):c.716G>A(p.Arg239His) variant causes a missense change. The variant allele was found at a frequency of 0.308 in 1,613,870 control chromosomes in the GnomAD database, including 88,987 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.43 (17398 hom., cov: 32)
  • Exomes 𝑓: 0.30 (71589 hom.)
• Consequence: FAM118A NM_017911.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.95

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.4712627E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM118A	NM_017911.4	c.716G>A	p.Arg239His	missense_variant	6/9	ENST00000441876.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM118A	ENST00000441876.7	c.716G>A	p.Arg239His	missense_variant	6/9	1	NM_017911.4	P1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64878 AN: 151958 Hom.: 17362 Cov.: 32

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.407

GnomAD3 exomes AF: 0.353 AC: 88875 AN: 251440 Hom.: 18139 AF XY: 0.349 AC XY: 47374 AN XY: 135904

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.372

Gnomad ASJ exome AF: 0.342

Gnomad EAS exome AF: 0.484

Gnomad SAS exome AF: 0.424

Gnomad FIN exome AF: 0.237

Gnomad NFE exome AF: 0.274

Gnomad OTH exome AF: 0.343

GnomAD4 exome AF: 0.296 AC: 432647 AN: 1461794 Hom.: 71589 Cov.: 37 AF XY: 0.298 AC XY: 216827 AN XY: 727202

Gnomad4 AFR exome AF: 0.770

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.427 AC: 64976 AN: 152076 Hom.: 17398 Cov.: 32 AF XY: 0.425 AC XY: 31584 AN XY: 74340

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.413

Alfa AF: 0.307 Hom.: 19775

Bravo AF: 0.452

TwinsUK AF: 0.258 AC: 958

ALSPAC AF: 0.261 AC: 1004

ESP6500AA AF: 0.743 AC: 3274

ESP6500EA AF: 0.271 AC: 2331

ExAC AF: 0.360 AC: 43725

Asia WGS AF: 0.504 AC: 1754 AN: 3478

EpiCase AF: 0.285

EpiControl AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
Cadd	Pathogenic	27
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.041	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.85	D
MetaRNN	Benign	0.0000055	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.0049	P;P;P
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.11
Sift	Benign	0.19	T;T
Sift4G	Benign	0.17	T;T
Polyphen		1.0	D;D
Vest4		0.13
MPC		0.87
ClinPred		0.031	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.040
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs6007594; hg19: chr22-45728370; COSMIC: COSV53416182; COSMIC: COSV53416182;