22-45328053-A-C

Variant names:

• chr22-45328053-A-C
• NM_017911.4:c.512A>C

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.512A>C​(p.Asp171Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D171V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM118A NM_017911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.87
• 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 (MetaRNN=0.2441397).

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.512A>C	p.Asp171Ala	missense	Exon 4 of 9	NP_060381.2	Q9NWS6-1
	FAM118A	NM_001349916.2		c.554A>C	p.Asp185Ala	missense	Exon 6 of 11	NP_001336845.1
	FAM118A	NM_001349914.2		c.515A>C	p.Asp172Ala	missense	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.512A>C	p.Asp171Ala	missense	Exon 4 of 9	ENSP00000395892.2	Q9NWS6-1
	FAM118A	ENST00000894424.1		c.515A>C	p.Asp172Ala	missense	Exon 5 of 10	ENSP00000564483.1
	FAM118A	ENST00000894426.1		c.515A>C	p.Asp172Ala	missense	Exon 4 of 9	ENSP00000564485.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1182866 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 594658

African (AFR) AF: 0.00 AC: 0 AN: 21634

American (AMR) AF: 0.00 AC: 0 AN: 36618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23486

East Asian (EAS) AF: 0.00 AC: 0 AN: 35036

South Asian (SAS) AF: 0.00 AC: 0 AN: 73418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5110

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 888056

Other (OTH) AF: 0.00 AC: 0 AN: 50026

GnomAD4 genome Cov.: 27

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Benign	0.029
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.38	B
Vest4		0.49
MutPred		0.41		Gain of MoRF binding (P = 0.0183)
MVP		0.61
MPC		0.25
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.52
gMVP		0.67
Mutation Taster		=25/75	disease causing

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

hg19: chr22-45723934;