rs6007594

Variant names:

• chr22-45332489-G-A
• rs6007594
• NM_017911.4:c.716G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-45332489-G-A
• chr22-45332489-G-C
• chr22-45332489-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349916.2(FAM118A):​c.758G>A​(p.Arg253His) 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.

• Frequency:
  • Genomes: 𝑓 0.43 (17398 hom., cov: 32)
  • Exomes 𝑓: 0.30 (71589 hom.)
• Consequence: FAM118A NM_001349916.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.95
• Publications: 58 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349916.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM118A	NM_017911.4	MANE Select	c.716G>A	p.Arg239His	missense	Exon 6 of 9	NP_060381.2
	FAM118A	NM_001349916.2		c.758G>A	p.Arg253His	missense	Exon 8 of 11	NP_001336845.1
	FAM118A	NM_001349914.2		c.719G>A	p.Arg240His	missense	Exon 6 of 9	NP_001336843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM118A	ENST00000441876.7	TSL:1 MANE Select	c.716G>A	p.Arg239His	missense	Exon 6 of 9	ENSP00000395892.2
	FAM118A	ENST00000894424.1		c.719G>A	p.Arg240His	missense	Exon 7 of 10	ENSP00000564483.1
	FAM118A	ENST00000894426.1		c.719G>A	p.Arg240His	missense	Exon 6 of 9	ENSP00000564485.1

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

GnomAD2 exomes AF: 0.353 AC: 88875 AN: 251440 AF XY: 0.349

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 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

African (AFR) AF: 0.770 AC: 25777 AN: 33476

American (AMR) AF: 0.375 AC: 16772 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 8726 AN: 26134

East Asian (EAS) AF: 0.465 AC: 18446 AN: 39696

South Asian (SAS) AF: 0.416 AC: 35908 AN: 86256

European-Finnish (FIN) AF: 0.238 AC: 12728 AN: 53418

Middle Eastern (MID) AF: 0.427 AC: 2463 AN: 5766

European-Non Finnish (NFE) AF: 0.262 AC: 291441 AN: 1111934

Other (OTH) AF: 0.338 AC: 20386 AN: 60390

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

African (AFR) AF: 0.752 AC: 31191 AN: 41482

American (AMR) AF: 0.418 AC: 6398 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1105 AN: 3472

East Asian (EAS) AF: 0.472 AC: 2441 AN: 5170

South Asian (SAS) AF: 0.429 AC: 2073 AN: 4828

European-Finnish (FIN) AF: 0.233 AC: 2457 AN: 10546

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18075 AN: 67972

Other (OTH) AF: 0.413 AC: 873 AN: 2116

Alfa AF: 0.331 Hom.: 36909

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 v4.9

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
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0000055	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.11
Sift	Benign	0.19	T
Sift4G	Benign	0.17	T
Polyphen		1.0	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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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