chr1-166070275-C-G

Variant names:

• chr1-166070275-C-G
• rs138713518
• NM_001017961.5:c.752G>C

Variant summary

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

The NM_001017961.5(FAM78B):​c.752G>C​(p.Arg251Pro) 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. 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. R251Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM78B NM_001017961.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.72
• Publications: 2 publications found

Genes affected

FAM78B (HGNC:13495): (family with sequence similarity 78 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=0.37812743).

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.752G>C	p.Arg251Pro	missense	Exon 2 of 2	NP_001017961.1	Q5VT40
	FAM78B	NM_001320302.2		c.264-9612G>C		intron	N/A	NP_001307231.1	F1T0K0
	FAM78B	NR_135199.2		n.1505G>C		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.752G>C	p.Arg251Pro	missense	Exon 2 of 2	ENSP00000346404.3	Q5VT40
	FAM78B	ENST00000338353.4	TSL:1	c.752G>C	p.Arg251Pro	missense	Exon 3 of 3	ENSP00000339681.3	Q5VT40
	FAM78B	ENST00000435676.2	TSL:2	n.728G>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000412766.1	H7C3M6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000483 AC: 1 AN: 207052 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000105

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	0.23	D
MutationAssessor	Benign	1.8	L
PhyloP100		4.7
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.56
Sift	Benign	0.27	T
Sift4G	Benign	0.33	T
Polyphen		0.96	D
Vest4		0.54
MutPred		0.34		Loss of MoRF binding (P = 0.0016)
MVP		0.47
MPC		1.9
ClinPred		0.83	D
GERP RS		3.9
Varity_R		0.50
gMVP		0.62
Mutation Taster		=61/39	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: rs138713518; hg19: chr1-166039512;