1-166070491-G-A

Variant names:

• chr1-166070491-G-A
• NM_001017961.5:c.536C>T
• FAM78B p.Thr179Ile

Variant summary

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

The NM_001017961.5(FAM78B):​c.536C>T​(p.Thr179Ile) 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 (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM78B NM_001017961.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.65
• Publications: 0 publications found

Genes affected

FAM78B (HGNC:13495): (family with sequence similarity 78 member B)

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=0.2191149).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017961.5. 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
	FAM78B	NM_001017961.5	MANE Select	c.536C>T	p.Thr179Ile	missense	Exon 2 of 2	NP_001017961.1	Q5VT40
	FAM78B	NM_001320302.2		c.264-9828C>T		intron	N/A	NP_001307231.1	F1T0K0
	FAM78B	NR_135199.2		n.1289C>T		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM78B	ENST00000354422.4	TSL:2 MANE Select	c.536C>T	p.Thr179Ile	missense	Exon 2 of 2	ENSP00000346404.3	Q5VT40
	FAM78B	ENST00000338353.4	TSL:1	c.536C>T	p.Thr179Ile	missense	Exon 3 of 3	ENSP00000339681.3	Q5VT40
	FAM78B	ENST00000435676.2	TSL:2	n.512C>T		non_coding_transcript_exon	Exon 2 of 3	ENSP00000412766.1	H7C3M6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.16
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.10
Sift	Benign	0.23	T
Sift4G	Uncertain	0.028	D
Varity_R		0.46
gMVP		0.35
Mutation Taster		=65/35	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-166039728;