9-131261322-C-T

Variant names:

• chr9-131261322-C-T
• rs139544612
• NM_033387.4:c.352G>A

Variant summary

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

The NM_033387.4(FAM78A):​c.352G>A​(p.Glu118Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,444,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E118Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM78A NM_033387.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90
• Publications: 0 publications found

Genes affected

FAM78A (HGNC:25465): (family with sequence similarity 78 member A)

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=0.14812562).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033387.4. 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
	FAM78A	NM_033387.4	MANE Select	c.352G>A	p.Glu118Lys	missense	Exon 2 of 2	NP_203745.2	Q5JUQ0
	FAM78A	NM_001399459.1		c.352G>A	p.Glu118Lys	missense	Exon 3 of 3	NP_001386388.1	Q5JUQ0
	FAM78A	NM_001400581.1		c.352G>A	p.Glu118Lys	missense	Exon 3 of 3	NP_001387510.1	Q5JUQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM78A	ENST00000372271.4	TSL:1 MANE Select	c.352G>A	p.Glu118Lys	missense	Exon 2 of 2	ENSP00000361345.3	Q5JUQ0
	FAM78A	ENST00000372269.7	TSL:1	c.343G>A	p.Glu115Lys	missense	Exon 4 of 4	ENSP00000361343.3	Q5JUQ2
	FAM78A	ENST00000704762.1		c.352G>A	p.Glu118Lys	missense	Exon 3 of 3	ENSP00000516028.1	Q5JUQ0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444620 Hom.: 0 Cov.: 34 AF XY: 0.00000139 AC XY: 1 AN XY: 718798

African (AFR) AF: 0.0000300 AC: 1 AN: 33282

American (AMR) AF: 0.00 AC: 0 AN: 43900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25656

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 85868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108968

Other (OTH) AF: 0.00 AC: 0 AN: 60032

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.033
Eigen_PC	Benign	0.098
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.073
Sift	Benign	0.15	T
Sift4G	Benign	0.14	T
Polyphen		0.84	P
Vest4		0.19
MutPred		0.32		Gain of ubiquitination at E118 (P = 0.0117)
MVP		0.32
MPC		0.85
ClinPred		0.49	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.16
Mutation Taster		=90/10	polymorphism

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: rs139544612; hg19: chr9-134136709;