ENST00000393526.6:c.-23C>G

Variant names:

• chr2-96894044-G-C
• rs774250251
• ENST00000393526.6:c.-23C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000393526.6(FAM178B):​c.-23C>G variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM178B ENST00000393526.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913
• Publications: 0 publications found

Genes affected

FAM178B (HGNC:28036): (family with sequence similarity 178 member B)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33921596).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393526.6. 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
	FAM178B	NM_001122646.3	MANE Select	c.1658C>G	p.Ser553Trp	missense	Exon 14 of 17	NP_001116118.2	Q8IXR5-3
	FAM178B	NM_016490.5		c.-23C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_057574.2
	FAM178B	NM_001172667.2		c.35C>G	p.Ser12Trp	missense	Exon 2 of 5	NP_001166138.1	Q8IXR5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM178B	ENST00000393526.6	TSL:1	c.-23C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000377160.2	Q8IXR5-2
	FAM178B	ENST00000490605.3	TSL:5 MANE Select	c.1658C>G	p.Ser553Trp	missense	Exon 14 of 17	ENSP00000429896.1	Q8IXR5-3
	FAM178B	ENST00000393526.6	TSL:1	c.-23C>G		5_prime_UTR	Exon 2 of 5	ENSP00000377160.2	Q8IXR5-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.97
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.75	T
PhyloP100		-0.91
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.13
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.019	D
Vest4		0.46
MVP		0.28
MPC		0.39
ClinPred		0.56	D
GERP RS		-5.4
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.2
gMVP		0.28
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs774250251; hg19: chr2-97559781;