22-45328016-C-A

Variant names:

• chr22-45328016-C-A
• rs367677553
• NM_017911.4:c.475C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017911.4(FAM118A):​c.475C>A​(p.Arg159Arg) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,574 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: FAM118A NM_017911.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.39
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017911.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM118A	NM_017911.4	MANE Select	c.475C>A	p.Arg159Arg	synonymous	Exon 4 of 9	NP_060381.2	Q9NWS6-1
	FAM118A	NM_001349916.2		c.517C>A	p.Arg173Arg	synonymous	Exon 6 of 11	NP_001336845.1
	FAM118A	NM_001349914.2		c.478C>A	p.Arg160Arg	synonymous	Exon 4 of 9	NP_001336843.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM118A	ENST00000441876.7	TSL:1 MANE Select	c.475C>A	p.Arg159Arg	synonymous	Exon 4 of 9	ENSP00000395892.2	Q9NWS6-1
	FAM118A	ENST00000894424.1		c.478C>A	p.Arg160Arg	synonymous	Exon 5 of 10	ENSP00000564483.1
	FAM118A	ENST00000894426.1		c.478C>A	p.Arg160Arg	synonymous	Exon 4 of 9	ENSP00000564485.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1457574 Hom.: 0 Cov.: 44 AF XY: 0.00000414 AC XY: 3 AN XY: 724884

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25994

East Asian (EAS) AF: 0.00 AC: 0 AN: 39342

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109900

Other (OTH) AF: 0.0000166 AC: 1 AN: 60220

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		7.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs367677553; hg19: chr22-45723897;