9-131261323-C-G

Variant names:

• chr9-131261323-C-G
• rs747962080
• NM_033387.4:c.351G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033387.4(FAM78A):​c.351G>C​(p.Gln117His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM78A NM_033387.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18934968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM78A	NM_033387.4	c.351G>C	p.Gln117His	missense_variant	Exon 2 of 2	ENST00000372271.4	NP_203745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM78A	ENST00000372271.4	c.351G>C	p.Gln117His	missense_variant	Exon 2 of 2	1	NM_033387.4	ENSP00000361345.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	.;T;.
Eigen	Benign	-0.032
Eigen_PC	Benign	0.025
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.69	.;N;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.92	N;N;N
REVEL	Benign	0.076
Sift	Uncertain	0.013	D;D;D
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.99	D;P;.
Vest4		0.11
MutPred		0.20		.;Gain of sheet (P = 0.1208);.;
MVP		0.26
MPC		1.1
ClinPred		0.73	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs747962080; hg19: chr9-134136710;