9-131261094-C-G

Variant names:

• chr9-131261094-C-G
• rs1478772865
• NM_033387.4:c.580G>C

Variant summary

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

The NM_033387.4(FAM78A):​c.580G>C​(p.Val194Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V194M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAM78A NM_033387.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.580G>C	p.Val194Leu	missense	Exon 2 of 2	NP_203745.2	Q5JUQ0
	FAM78A	NM_001399459.1		c.580G>C	p.Val194Leu	missense	Exon 3 of 3	NP_001386388.1	Q5JUQ0
	FAM78A	NM_001400581.1		c.580G>C	p.Val194Leu	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.580G>C	p.Val194Leu	missense	Exon 2 of 2	ENSP00000361345.3	Q5JUQ0
	FAM78A	ENST00000372269.7	TSL:1	c.571G>C	p.Val191Leu	missense	Exon 4 of 4	ENSP00000361343.3	Q5JUQ2
	FAM78A	ENST00000704762.1		c.580G>C	p.Val194Leu	missense	Exon 3 of 3	ENSP00000516028.1	Q5JUQ0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461822 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.9
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N
REVEL	Pathogenic	0.79
Sift	Benign	0.058	T
Sift4G	Benign	0.11	T
Polyphen		0.99	D
Vest4		0.79
MutPred		0.49		Loss of sheet (P = 0.0104)
MVP		0.85
MPC		1.8
ClinPred		0.91	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.81
Mutation Taster		=39/61	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

dbSNP: rs1478772865; hg19: chr9-134136481;